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Morimoto K, Yamanaka S, Matsui K, Kinoshita Y, Inage Y, Yamamoto S, Koda N, Matsumoto N, Saito Y, Takamura T, Fujimoto T, Fukunaga S, Tajiri S, Matsumoto K, Ozawa K, Wada S, Kobayashi E, Yokoo T. Fetal-to-fetal kidney transplantation in utero. Commun Biol 2025; 8:349. [PMID: 40033127 PMCID: PMC11876676 DOI: 10.1038/s42003-025-07783-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2024] [Accepted: 02/19/2025] [Indexed: 03/05/2025] Open
Abstract
Potter sequence consists of various symptoms associated with renal dysplasia. For bilateral renal agenesis, there is no hope of survival. As a novel therapeutic approach for Potter sequence, we develop a unique approach of "transplantation of fetal kidneys from a different species during the fetal stage." In this study, we first validate the approach using allogeneic transplantation. Fetal kidneys with bladders from green fluorescent protein-expressing rats (embryonic day 14.0-16.5) are subcutaneously transplanted into allogeneic rat fetuses in utero (embryonic day 18.0-18.5). After birth, the transplanted fetal kidneys are confirmed to have urine production capability. Furthermore, long-term (up to 150 days) urine production is sustained. Next, we perform xenotransplantation. The transplantation of mouse fetal kidneys into rat fetuses in utero leads to the maturation of renal tissue structures. We demonstrate organ transplantation into in utero fetuses using fetal kidneys as donor organs for fetal therapy.
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Affiliation(s)
- Keita Morimoto
- Division of Nephrology and Hypertension, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, 105-8461, Japan
| | - Shuichiro Yamanaka
- Division of Nephrology and Hypertension, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, 105-8461, Japan.
- Kidney Applied Regenerative Medicine, Project Research Units, The Jikei University School of Medicine, Tokyo, 105-8461, Japan.
| | - Kenji Matsui
- Division of Nephrology and Hypertension, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, 105-8461, Japan
| | - Yoshitaka Kinoshita
- Division of Nephrology and Hypertension, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, 105-8461, Japan
- Department of Urology, Graduate School of Medicine, The University of Tokyo, Tokyo, 113-8654, Japan
| | - Yuka Inage
- Division of Nephrology and Hypertension, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, 105-8461, Japan
- Department of Pediatrics, The Jikei University School of Medicine, Tokyo, 105-8461, Japan
| | - Shutaro Yamamoto
- Department of Urology, The Jikei University School of Medicine, Tokyo, 105-8461, Japan
| | - Nagisa Koda
- Division of Nephrology and Hypertension, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, 105-8461, Japan
| | - Naoto Matsumoto
- Division of Nephrology and Hypertension, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, 105-8461, Japan
| | - Yatsumu Saito
- Division of Nephrology and Hypertension, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, 105-8461, Japan
| | - Tsuyoshi Takamura
- Division of Nephrology and Hypertension, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, 105-8461, Japan
| | - Toshinari Fujimoto
- Division of Nephrology and Hypertension, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, 105-8461, Japan
| | - Shohei Fukunaga
- Division of Nephrology and Hypertension, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, 105-8461, Japan
| | - Susumu Tajiri
- Division of Nephrology and Hypertension, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, 105-8461, Japan
| | - Kei Matsumoto
- Division of Nephrology and Hypertension, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, 105-8461, Japan
| | - Katsusuke Ozawa
- Center for Maternal-Fetal, Neonatal and Reproductive Medicine, National Center for Child Health and Development, Tokyo, 157-8535, Japan
| | - Seiji Wada
- Center for Maternal-Fetal, Neonatal and Reproductive Medicine, National Center for Child Health and Development, Tokyo, 157-8535, Japan
| | - Eiji Kobayashi
- Department of Kidney Regenerative Medicine, The Jikei University School of Medicine, Tokyo, 105-8461, Japan
| | - Takashi Yokoo
- Division of Nephrology and Hypertension, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, 105-8461, Japan.
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Jammes M, Tabasi A, Bach T, Ritter T. Healing the cornea: Exploring the therapeutic solutions offered by MSCs and MSC-derived EVs. Prog Retin Eye Res 2025; 105:101325. [PMID: 39709150 DOI: 10.1016/j.preteyeres.2024.101325] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/18/2024] [Revised: 12/16/2024] [Accepted: 12/17/2024] [Indexed: 12/23/2024]
Abstract
Affecting a large proportion of the population worldwide, corneal disorders constitute a concerning health hazard associated to compromised eyesight or blindness for most severe cases. In the last decades, mesenchymal stem/stromal cells (MSCs) demonstrated promising abilities in improving symptoms associated to corneal diseases or alleviating these affections, especially through their anti-inflammatory, immunomodulatory and pro-regenerative properties. More recently, MSC therapeutic potential was shown to be mediated by the molecules they release, and particularly by their extracellular vesicles (EVs; MSC-EVs). Consequently, using MSC-EVs emerged as a pioneering strategy to mitigate the risks related to cell therapy while providing MSC therapeutic benefits. Despite the promises given by MSC- and MSC-EV-based approaches, many improvements are considered to optimize the therapeutic significance of these therapies. This review aspires to provide a comprehensive and detailed overview of current knowledge on corneal therapies involving MSCs and MSC-EVs, the strategies currently under evaluation, and the gaps remaining to be addressed for clinical implementation. From encapsulating MSCs or their EVs into biomaterials to enhance the ocular retention time to loading MSC-EVs with therapeutic drugs, a wide range of ground-breaking strategies are currently contemplated to lead to the safest and most effective treatments. Promising research initiatives also include diverse gene therapies and the targeting of specific cell types through the modification of the EV surface, paving the way for future therapeutic innovations. As one of the most important challenges, MSC-EV large-scale production strategies are extensively investigated and offer a wide array of possibilities to meet the needs of clinical applications.
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Affiliation(s)
- Manon Jammes
- Regenerative Medicine Institute, School of Medicine, University of Galway, Galway, Ireland
| | - Abbas Tabasi
- Regenerative Medicine Institute, School of Medicine, University of Galway, Galway, Ireland
| | - Trung Bach
- Regenerative Medicine Institute, School of Medicine, University of Galway, Galway, Ireland
| | - Thomas Ritter
- Regenerative Medicine Institute, School of Medicine, University of Galway, Galway, Ireland; CURAM Centre for Research in Medical Devices, University of Galway, Galway, Ireland.
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Vo QD, Nakamura K, Saito Y, Iida T, Yoshida M, Amioka N, Akagi S, Miyoshi T, Yuasa S. iPSC-Derived Biological Pacemaker-From Bench to Bedside. Cells 2024; 13:2045. [PMID: 39768137 PMCID: PMC11674228 DOI: 10.3390/cells13242045] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/11/2024] [Revised: 12/08/2024] [Accepted: 12/09/2024] [Indexed: 01/11/2025] Open
Abstract
Induced pluripotent stem cell (iPSC)-derived biological pacemakers have emerged as an alternative to traditional electronic pacemakers for managing cardiac arrhythmias. While effective, electronic pacemakers face challenges such as device failure, lead complications, and surgical risks, particularly in children. iPSC-derived pacemakers offer a promising solution by mimicking the sinoatrial node's natural pacemaking function, providing a more physiological approach to rhythm control. These cells can differentiate into cardiomyocytes capable of autonomous electrical activity, integrating into heart tissue. However, challenges such as achieving cellular maturity, long-term functionality, and immune response remain significant barriers to clinical translation. Future research should focus on refining gene-editing techniques, optimizing differentiation, and developing scalable production processes to enhance the safety and effectiveness of these biological pacemakers. With further advancements, iPSC-derived pacemakers could offer a patient-specific, durable alternative for cardiac rhythm management. This review discusses key advancements in differentiation protocols and preclinical studies, demonstrating their potential in treating dysrhythmias.
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Affiliation(s)
- Quan Duy Vo
- Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 700-8558, Japan; (Q.D.V.); (T.I.); (M.Y.); (S.A.); (T.M.); (S.Y.)
| | - Kazufumi Nakamura
- Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 700-8558, Japan; (Q.D.V.); (T.I.); (M.Y.); (S.A.); (T.M.); (S.Y.)
- Center for Advanced Heart Failure, Okayama University Hospital, Okayama 700-8558, Japan
| | - Yukihiro Saito
- Department of Cardiovascular Medicine, Okayama University Hospital, Okayama 700-8558, Japan; (Y.S.); (N.A.)
| | - Toshihiro Iida
- Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 700-8558, Japan; (Q.D.V.); (T.I.); (M.Y.); (S.A.); (T.M.); (S.Y.)
| | - Masashi Yoshida
- Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 700-8558, Japan; (Q.D.V.); (T.I.); (M.Y.); (S.A.); (T.M.); (S.Y.)
| | - Naofumi Amioka
- Department of Cardiovascular Medicine, Okayama University Hospital, Okayama 700-8558, Japan; (Y.S.); (N.A.)
| | - Satoshi Akagi
- Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 700-8558, Japan; (Q.D.V.); (T.I.); (M.Y.); (S.A.); (T.M.); (S.Y.)
| | - Toru Miyoshi
- Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 700-8558, Japan; (Q.D.V.); (T.I.); (M.Y.); (S.A.); (T.M.); (S.Y.)
| | - Shinsuke Yuasa
- Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 700-8558, Japan; (Q.D.V.); (T.I.); (M.Y.); (S.A.); (T.M.); (S.Y.)
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Bu Z, Lou J, Xu W, Zhang L, Tang Y. Human umbilical cord mesenchymal stem cell-based gene therapy for hemophilia B using scAAV-DJ/8-LP1-hFIXco transduction. Stem Cell Res Ther 2024; 15:210. [PMID: 39020429 PMCID: PMC11256413 DOI: 10.1186/s13287-024-03824-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2024] [Accepted: 07/01/2024] [Indexed: 07/19/2024] Open
Abstract
BACKGROUND Hemophilia B is an X-linked bleeding disorder caused by a mutation in the gene responsible for encoding coagulation factor IX (FIX). Gene therapy offers promising potential for curing this disease. However, the current method of relatively high dosage of virus injection carries inherent risks. The purpose of this study was to introduce a novel scAAV-DJ/8-LP1-hFIXco vector transduced human umbilical cord blood derived mesenchymal stem cells (HUCMSCs) as an alternative cell-based gene therapy to conventional gene therapy for Hemophilia B. METHODS The LP1-hFIXco gene structure was designed by us through searching the literature from NCBI and the scAAV-DJ/8-LP1-hFIXco vector was constructed by a commercial company. The HUCMSCs were cultivated in routine approach and transduced with scAAV-DJ/8-LP1-hFIXco vector. The human FIX activation system was employed for detection of hFIXco activity. The RNA and protein expression levels of the hFIXco were evaluated using PCR and western blot techniques. In animal studies, both NSG and F9-KO mice were used for the experiment, in which clotting time was utilized as a parameter for bleeding assessment. The immunohistochemical analysis was used to assess the distribution of HUCMSCs in mouse tissue sections. The safety for tumorigenicity of this cell-based gene therapy was evaluated by pathological observation after hematoxylin-eosin staining. RESULTS The transduction of HUCMSCs with the scAAV-DJ/8-LP1-hFIXco vector results in consistent and sustainable secretion of human FIXco during 5 months period both in vitro and in mouse model. The secretion level (hFIXco activity: 97.1 ± 2.3% at day 7 to 48.8 ± 4.5% at 5 months) was comparable to that observed following intravenous injection with a high dose of the viral vector (hFIXco activity: 95.2 ± 2.2% to 40.8 ± 4.3%). After a 5-month observation period, no clonal expansions of the transduced cells in tissues were observed in any of the mice studied. CONCLUSIONS We have discovered a novel and safer HUCMSCs mediated approach potentially effective for gene therapy in hemophilia B.
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Affiliation(s)
- Zibin Bu
- Division/Center of Hematology-oncology, Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Zhejiang Hangzhou, 310003, PR China
| | - Jintu Lou
- Department of Clinical Laboratory, Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Zhejiang Hangzhou, 310003, PR China
| | - Weiqun Xu
- Division/Center of Hematology-oncology, Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Zhejiang Hangzhou, 310003, PR China
| | - Lingyan Zhang
- Division/Center of Hematology-oncology, Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Zhejiang Hangzhou, 310003, PR China
| | - Yongmin Tang
- Division/Center of Hematology-oncology, Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Zhejiang Hangzhou, 310003, PR China.
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Zhang N, Shu L, Liu Z, Shi A, Zhao L, Huang S, Sheng G, Yan Z, Song Y, Huang F, Tang Y, Zhang Z. The role of extracellular vesicles in cholangiocarcinoma tumor microenvironment. Front Pharmacol 2024; 14:1336685. [PMID: 38269274 PMCID: PMC10805838 DOI: 10.3389/fphar.2023.1336685] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/11/2023] [Accepted: 12/26/2023] [Indexed: 01/26/2024] Open
Abstract
Cholangiocarcinoma (CCA) is a highly aggressive malignant tumor that originates from the biliary system. With restricted treatment options at hand, the challenging aspect of early CCA diagnosis leads to a bleak prognosis. Besides the intrinsic characteristics of tumor cells, the generation and progression of CCA are profoundly influenced by the tumor microenvironment, which engages in intricate interactions with cholangiocarcinoma cells. Of notable significance is the role of extracellular vesicles as key carriers in enabling communication between cancer cells and the tumor microenvironment. This review aims to provide a comprehensive overview of current research examining the interplay between extracellular vesicles and the tumor microenvironment in the context of CCA. Specifically, we will emphasize the significant contributions of extracellular vesicles in molding the CCA microenvironment and explore their potential applications in the diagnosis, prognosis assessment, and therapeutic strategies for this aggressive malignancy.
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Affiliation(s)
- Nuoqi Zhang
- Department of General Surgery, Qilu Hospital, Shandong University, Jinan, Shandong, China
| | - Lizhuang Shu
- Department of General Surgery, Qilu Hospital, Shandong University, Jinan, Shandong, China
| | - Zengli Liu
- Department of General Surgery, Qilu Hospital, Shandong University, Jinan, Shandong, China
- Department of General Surgery, Qilu Hospital, Shandong University, Qingdao, Shandong, China
| | - Anda Shi
- Department of General Surgery, Qilu Hospital, Shandong University, Jinan, Shandong, China
| | - Liming Zhao
- Department of General Surgery, Qilu Hospital, Shandong University, Jinan, Shandong, China
| | - Shaohui Huang
- Department of General Surgery, Qilu Hospital, Shandong University, Jinan, Shandong, China
| | - Guoli Sheng
- Department of General Surgery, Qilu Hospital, Shandong University, Jinan, Shandong, China
| | - Zhangdi Yan
- Department of General Surgery, Qilu Hospital, Shandong University, Jinan, Shandong, China
| | - Yan Song
- Department of General Surgery, Qilu Hospital, Shandong University, Jinan, Shandong, China
| | - Fan Huang
- Department of General Surgery, Qilu Hospital, Shandong University, Jinan, Shandong, China
| | - Yongchang Tang
- Department of General Surgery, Qilu Hospital, Shandong University, Jinan, Shandong, China
| | - Zongli Zhang
- Department of General Surgery, Qilu Hospital, Shandong University, Jinan, Shandong, China
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Huang B, Fu S, Hao Y, Yeung CK, Zhang X, Li E, Xu X, Shao N, Xu RH. Developmental potency of human ES cell-derived mesenchymal stem cells revealed in mouse embryos following blastocyst injection. Cell Rep 2023; 42:113459. [PMID: 37988266 DOI: 10.1016/j.celrep.2023.113459] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2023] [Revised: 08/26/2023] [Accepted: 11/02/2023] [Indexed: 11/23/2023] Open
Abstract
Mesenchymal stem cells (MSCs) are present in almost all the tissues in the body, critical for their homeostasis and regeneration. However, the stemness of MSCs is mainly an in vitro observation, and lacking exclusive markers for endogenous MSCs makes it difficult to study the multipotency of MSCs in vivo, especially for human MSCs. To address this hurdle, we injected GFP-tagged human embryonic stem cell (hESC)-derived MSCs (EMSCs) into mouse blastocysts. EMSCs survived well and penetrated both the inner cell mass and trophectoderm, correlating to the higher anti-apoptotic capability of EMSCs than hESCs. Injected EMSCs contributed to skeletal, dermal, and extraembryonic tissues in the resultant chimera and partially rescued skeletal defects in Sox9+/- mouse fetuses. Thus, this study provides evidence for the stemness and developmental capability of human MSCs through chimerization with the mouse blastocyst, serving as a model for studying human mesenchymal and skeletal development.
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Affiliation(s)
- Borong Huang
- Center of Reproduction, Development & Aging, and Institute of Translational Medicine, Faculty of Health Sciences, University of Macau, Taipa, Macau, China
| | - Siyi Fu
- Center of Reproduction, Development & Aging, and Institute of Translational Medicine, Faculty of Health Sciences, University of Macau, Taipa, Macau, China
| | - Yanan Hao
- Center of Reproduction, Development & Aging, and Institute of Translational Medicine, Faculty of Health Sciences, University of Macau, Taipa, Macau, China
| | - Cheung Kwan Yeung
- Center of Reproduction, Development & Aging, and Institute of Translational Medicine, Faculty of Health Sciences, University of Macau, Taipa, Macau, China
| | - Xin Zhang
- Center of Reproduction, Development & Aging, and Institute of Translational Medicine, Faculty of Health Sciences, University of Macau, Taipa, Macau, China
| | - Enqin Li
- Center of Reproduction, Development & Aging, and Institute of Translational Medicine, Faculty of Health Sciences, University of Macau, Taipa, Macau, China
| | - Xiaoling Xu
- Center of Reproduction, Development & Aging, and Institute of Translational Medicine, Faculty of Health Sciences, University of Macau, Taipa, Macau, China
| | - Ningyi Shao
- Center of Reproduction, Development & Aging, and Institute of Translational Medicine, Faculty of Health Sciences, University of Macau, Taipa, Macau, China
| | - Ren-He Xu
- Center of Reproduction, Development & Aging, and Institute of Translational Medicine, Faculty of Health Sciences, University of Macau, Taipa, Macau, China.
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Takagi R, Takegaki J, Osana S, Kano Y, Konishi S, Fujita S. Cooling-promoted myogenic differentiation of murine bone marrow mesenchymal stem cells through TRPM8 activation in vitro. Physiol Rep 2023; 11:e15855. [PMID: 38086691 PMCID: PMC10716030 DOI: 10.14814/phy2.15855] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2023] [Revised: 10/19/2023] [Accepted: 10/19/2023] [Indexed: 12/17/2023] Open
Abstract
TRPM8 agonist has been reported to promote osteogenic differentiation of mesenchymal stem cells (MSCs), therefore we evaluated whether cooling-induced activation of TRPM8 promotes myogenic differentiation of MSCs. We used 5-azacytidine as a myogenic differentiation inducer in murine bone marrow-derived MSCs. Addition of menthol, a TRPM8 agonist, to the differentiation induction medium significantly, increased the percentage of MyoD-positive cells, a specific marker of myogenic differentiation. We performed intracellular Ca2+ imaging experiments using fura-2 to confirm TRPM8 activation by cooling stimulation. The results confirmed that intracellular Ca2+ concentration ([Ca2+ ]i) increases due to TRPM8 activation, and TRPM8 antagonist inhibits increase in [Ca2+ ]i at medium temperatures below 19°C. We also examined the effect of cooling exposure time on myogenic differentiation of MSCs using an external cooling stimulus set at 17°C. The results showed that 60 min of cooling had an acceleratory effect on differentiation (2.18 ± 0.27 times). We observed that the TRPM8 antagonist counteracted the differentiation-promoting effect of the cooling. These results suggest that TRPM8 might modulate the multiple differentiation pathways of MSCs, and that cooling is an effective way of activating TRPM8, which regulates MSCs differentiation in vitro.
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Affiliation(s)
- Ryo Takagi
- Ritsumeikan Global Innovation Research OrganizationRitsumeikan UniversityShigaJapan
| | - Junya Takegaki
- Research Organization of Science and TechnologyRitsumeikan UniversityShigaJapan
| | - Shion Osana
- Graduate School of Informatics and EngineeringUniversity of Electro‐CommunicationsTokyoJapan
- Faculty of Physical Education, Department of Sport and Medical ScienceKokushikan UniversityTokyoJapan
| | - Yutaka Kano
- Graduate School of Informatics and EngineeringUniversity of Electro‐CommunicationsTokyoJapan
- Center for Neuroscience and Biomedical EngineeringUniversity of Electro‐CommunicationsTokyoJapan
| | - Satoshi Konishi
- Faculty of Science and EngineeringRitsumeikan UniversityShigaJapan
| | - Satoshi Fujita
- Faculty of Sport and Health ScienceRitsumeikan UniversityShigaJapan
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Liu CM, Chen YC, Hu YF. Harnessing cell reprogramming for cardiac biological pacing. J Biomed Sci 2023; 30:74. [PMID: 37633890 PMCID: PMC10463311 DOI: 10.1186/s12929-023-00970-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/06/2023] [Accepted: 08/22/2023] [Indexed: 08/28/2023] Open
Abstract
Electrical impulses from cardiac pacemaker cardiomyocytes initiate cardiac contraction and blood pumping and maintain life. Abnormal electrical impulses bring patients with low heart rates to cardiac arrest. The current therapy is to implant electronic devices to generate backup electricity. However, complications inherent to electronic devices remain unbearable suffering. Therefore, cardiac biological pacing has been developed as a hardware-free alternative. The approaches to generating biological pacing have evolved recently using cell reprogramming technology to generate pacemaker cardiomyocytes in-vivo or in-vitro. Different from conventional methods by electrical re-engineering, reprogramming-based biological pacing recapitulates various phenotypes of de novo pacemaker cardiomyocytes and is more physiological, efficient, and easy for clinical implementation. This article reviews the present state of the art in reprogramming-based biological pacing. We begin with the rationale for this new approach and review its advances in creating a biological pacemaker to treat bradyarrhythmia.
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Affiliation(s)
- Chih-Min Liu
- Division of Cardiology, Department of Medicine, Heart Rhythm Center, Taipei Veterans General Hospital, Taipei, Taiwan
- Faculty of Medicine and Institute of Clinical Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
| | - Yi-Chun Chen
- Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan
- Institute of Biopharmaceutical Sciences, College of Pharmaceutical Sciences, National Yang Ming Chiao Tung University, Taipei, Taiwan
| | - Yu-Feng Hu
- Division of Cardiology, Department of Medicine, Heart Rhythm Center, Taipei Veterans General Hospital, Taipei, Taiwan.
- Faculty of Medicine and Institute of Clinical Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan.
- Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.
- Institute of Biopharmaceutical Sciences, College of Pharmaceutical Sciences, National Yang Ming Chiao Tung University, Taipei, Taiwan.
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Jing Y, Zhou J, Guo F, Yu L, Ren X, Yin X. Betaine regulates adipogenic and osteogenic differentiation of hAD-MSCs. Mol Biol Rep 2023; 50:5081-5089. [PMID: 37101008 DOI: 10.1007/s11033-023-08404-6] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2023] [Accepted: 03/23/2023] [Indexed: 04/28/2023]
Abstract
BACKGROUND With an ageing population, the incidence of bone loss and obesity are increasing. Numerous studies emphasized the multidirectional differentiation ability of mesenchymal stem cells (MSCs), and reported betaine modulated the osteogenic differentiation and adipogenic differentiation of MSCs in vitro. We wondered how betaine affected the differentiation of hAD-MSCs and hUC-MSCs. METHODS AND RESULTS ALP staining and alizarin red S (ARS) staining were proved 10 mM betaine significantly increased the number of ALP-positive cells and plaque calcified extracellular matrices, accompanying by the up-regulation of OPN, Runx-2 and OCN. Oil red O staining demonstrated the number and size of lipid droplets were reduced, the expression of adipogenic master genes such as PPARγ, CEBPα and FASN were down-regulated simultaneously. For further investigating the mechanism of betaine on hAD-MSCs, RNA-seq was performed in none-differentiation medium. The Gene Ontology (GO) analysis showed fat cell differentiation and bone mineralization function terms were enriched, and KEGG showed PI3K-Akt signaling pathway, cytokine-cytokine receptor interaction and ECM-receptor interaction pathways were enriched in betaine treated hAD-MSCs, demonstrated betaine had a positive inducing effect on osteogenic of hAD-MSCs in the non-differentiation medium in vitro, which is opposite to the effect on adipogenic differentiation. CONCLUSIONS Our study demonstrated that betaine promoted osteogenic and compromised adipogenic differentiation of hUC-MSCs and hAD-MSCs upon low concentration administration. PI3K-Akt signaling pathway, cytokine-cytokine receptor interaction and ECM-receptor interaction were significantly enriched under betaine-treated. We showed hAD-MSCs were more sensitive to betaine stimulation and have a better differentiation ability than hUC-MSCs. Our results contributed to the exploration of betaine as an aiding agent for MSCs therapy.
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Affiliation(s)
- Yue Jing
- Applied Biology Laboratory, College of Pharmaceutical and Biological Engineering, Shenyang University of Chemical Technology, Shenyang, Liaoning Province, China
| | - Jian Zhou
- College of Pharmaceutical Sciences, Gannan Medical University, Ganzhou, Jiangxi Province, China
| | - Fenghua Guo
- Jiangsu Pulu Rui Medical Technology Co., Ltd, Xuzhou, Jiangsu Province, China
| | - Lin Yu
- Applied Biology Laboratory, College of Pharmaceutical and Biological Engineering, Shenyang University of Chemical Technology, Shenyang, Liaoning Province, China
| | - Xiaomeng Ren
- Applied Biology Laboratory, College of Pharmaceutical and Biological Engineering, Shenyang University of Chemical Technology, Shenyang, Liaoning Province, China
| | - Xiushan Yin
- Applied Biology Laboratory, College of Pharmaceutical and Biological Engineering, Shenyang University of Chemical Technology, Shenyang, Liaoning Province, China.
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Yu Q, Wang Q, Zhang L, Deng W, Cao X, Wang Z, Sun X, Yu J, Xu X. The applications of 3D printing in wound healing: the external delivery of stem cells and antibiosis. Adv Drug Deliv Rev 2023; 197:114823. [PMID: 37068658 DOI: 10.1016/j.addr.2023.114823] [Citation(s) in RCA: 14] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2022] [Revised: 04/07/2023] [Accepted: 04/11/2023] [Indexed: 04/19/2023]
Abstract
As the global number of chronic wound patients rises, the financial burden and social pressure on patients increase daily. Stem cells have emerged as promising tissue engineering seed cells due to their enriched sources, multidirectional differentiation ability, and high proliferation rate. However, delivering them in vitro for the treatment of skin injury is still challenging. In addition, bacteria from the wound site and the environment can significantly impact wound healing. In the last decade, 3D bioprinting has dramatically enriched cell delivery systems. The produced scaffolds by this technique can be precisely localized within cells and perform antibacterial actions. In this review, we summarized the 3D bioprinting-based external delivery of stem cells and their antibiosis to improve wound healing.
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Affiliation(s)
- Qingtong Yu
- School of Pharmacy, Jiangsu University, Zhenjiang 212013, PR China
| | - Qilong Wang
- School of Pharmacy, Jiangsu University, Zhenjiang 212013, PR China
| | - Linzhi Zhang
- School of Pharmacy, Jiangsu University, Zhenjiang 212013, PR China
| | - Wenwen Deng
- School of Pharmacy, Jiangsu University, Zhenjiang 212013, PR China
| | - Xia Cao
- School of Pharmacy, Jiangsu University, Zhenjiang 212013, PR China
| | - Zhe Wang
- School of Pharmacy, Jiangsu University, Zhenjiang 212013, PR China
| | - Xuan Sun
- School of Pharmacy, Jiangsu University, Zhenjiang 212013, PR China
| | - Jiangnan Yu
- School of Pharmacy, Jiangsu University, Zhenjiang 212013, PR China
| | - Ximing Xu
- School of Pharmacy, Jiangsu University, Zhenjiang 212013, PR China.
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11
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Rao JS, Pruett TL. Immunology of the transplanted cryopreserved kidney. Cryobiology 2023; 110:1-7. [PMID: 36640932 DOI: 10.1016/j.cryobiol.2023.01.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2022] [Revised: 12/28/2022] [Accepted: 01/10/2023] [Indexed: 01/13/2023]
Abstract
Transplantation has substituted dysfunctional organs with healthy organs from donors to significantly lower morbidity and mortality associated with end-stage organ disease. Since the advent of transplantation, the promise of functional replacement has attracted an exponential mismatch between organ supply and demand. Theoretical proposals to counter the increasing needs have either been to create a source through genetic engineering of porcine donors for xenotransplantation (with more potent immunosuppression protocols) or recreate one's organ in a pig using interspecies blastocyst complementation for exogenic organ transplantation (without immunosuppression). Another promising avenue has been organ banking through cryopreservation for transplantation. Although ice free preservation and acceptable early function following rewarming is critical for success in transplantation, the immunological response that predominantly defines short- and long-term graft survival has failed to captivate attention to date. It is well sorted that thermal and metabolic stress incurred at 4 °C during recovery and reperfusion of organs for clinical transplantation has varying impact on graft survival. Considering the magnitude of cellular imbalance and injury at sub-zero/ultralow temperatures in addition to the chemical toxicity of cryoprotective agents (CPA), it is essential to assess and address the immunological response associated following transplantation to maximize the success of cryopreservation.
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Affiliation(s)
- Joseph Sushil Rao
- Division of Solid Organ Transplantation, Department of Surgery, University of Minnesota, Minneapolis, MN, USA; Schulze Diabetes Institute, Department of Surgery, University of Minnesota, Minneapolis, MN, USA.
| | - Timothy L Pruett
- Division of Solid Organ Transplantation, Department of Surgery, University of Minnesota, Minneapolis, MN, USA.
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12
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Sarmah H, Sawada A, Hwang Y, Miura A, Shimamura Y, Tanaka J, Yamada K, Mori M. Towards human organ generation using interspecies blastocyst complementation: Challenges and perspectives for therapy. Front Cell Dev Biol 2023; 11:1070560. [PMID: 36743411 PMCID: PMC9893295 DOI: 10.3389/fcell.2023.1070560] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/15/2022] [Accepted: 01/05/2023] [Indexed: 01/20/2023] Open
Abstract
Millions of people suffer from end-stage refractory diseases. The ideal treatment option for terminally ill patients is organ transplantation. However, donor organs are in absolute shortage, and sadly, most patients die while waiting for a donor organ. To date, no technology has achieved long-term sustainable patient-derived organ generation. In this regard, emerging technologies of chimeric human organ production via blastocyst complementation (BC) holds great promise. To take human organ generation via BC and transplantation to the next step, we reviewed current emerging organ generation technologies and the associated efficiency of chimera formation in human cells from the standpoint of developmental biology.
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Affiliation(s)
- Hemanta Sarmah
- Department of Medicine, Columbia Center for Human Development, Columbia University Medical Center, New York, NY, United States
| | - Anri Sawada
- Department of Medicine, Columbia Center for Human Development, Columbia University Medical Center, New York, NY, United States
| | - Youngmin Hwang
- Department of Medicine, Columbia Center for Human Development, Columbia University Medical Center, New York, NY, United States
| | - Akihiro Miura
- Department of Medicine, Columbia Center for Human Development, Columbia University Medical Center, New York, NY, United States
| | - Yuko Shimamura
- Department of Medicine, Columbia Center for Human Development, Columbia University Medical Center, New York, NY, United States
| | - Junichi Tanaka
- Department of Medicine, Columbia Center for Human Development, Columbia University Medical Center, New York, NY, United States
| | - Kazuhiko Yamada
- Department of Surgery, Johns Hopkins University, Baltimore, MD, United States
| | - Munemasa Mori
- Department of Medicine, Columbia Center for Human Development, Columbia University Medical Center, New York, NY, United States
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13
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Chae S, Yong U, Park W, Choi YM, Jeon IH, Kang H, Jang J, Choi HS, Cho DW. 3D cell-printing of gradient multi-tissue interfaces for rotator cuff regeneration. Bioact Mater 2023; 19:611-625. [PMID: 35600967 PMCID: PMC9109128 DOI: 10.1016/j.bioactmat.2022.05.004] [Citation(s) in RCA: 20] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/04/2022] [Revised: 05/02/2022] [Accepted: 05/02/2022] [Indexed: 12/21/2022] Open
Abstract
Owing to the prevalence of rotator cuff (RC) injuries and suboptimal healing outcome, rapid and functional regeneration of the tendon–bone interface (TBI) after RC repair continues to be a major clinical challenge. Given the essential role of the RC in shoulder movement, the engineering of biomimetic multi-tissue constructs presents an opportunity for complex TBI reconstruction after RC repair. Here, we propose a gradient cell-laden multi-tissue construct combined with compositional gradient TBI-specific bioinks via 3D cell-printing technology. In vitro studies demonstrated the capability of a gradient scaffold system in zone-specific inducibility and multi-tissue formation mimicking TBI. The regenerative performance of the gradient scaffold on RC regeneration was determined using a rat RC repair model. In particular, we adopted nondestructive, consecutive, and tissue-targeted near-infrared fluorescence imaging to visualize the direct anatomical change and the intricate RC regeneration progression in real time in vivo. Furthermore, the 3D cell-printed implant promotes effective restoration of shoulder locomotion function and accelerates TBI healing in vivo. In summary, this study identifies the therapeutic contribution of cell-printed constructs towards functional RC regeneration, demonstrating the translational potential of biomimetic gradient constructs for the clinical repair of multi-tissue interfaces.
A biomimetic cellular TBI scaffold was 3D bioprinted with dECM bioinks. A gradient multi-tissue construct was implanted for RC repair in vivo. Targeted NIR fluorescence imaging facilitated real-time monitoring of TBI regeneration. The scaffolds had therapeutic contribution on gradient TBI regeneration and functional recovery.
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Affiliation(s)
- Suhun Chae
- Department of Mechanical Engineering, Pohang University of Science and Technology, 77 Cheongam-ro, Nam-gu, Gyeongsangbuk-do, Pohang, 37673, South Korea
- EDmicBio Inc., 111 Hoegi-ro, Dongdaemun-gu, Seoul 02445, South Korea
| | - Uijung Yong
- Department of Convergence IT Engineering, Pohang University of Science and Technology, 77 Cheongam-ro, Nam-gu, Gyeongsangbuk-do, Pohang, 37673, South Korea
| | - Wonbin Park
- Department of Mechanical Engineering, Pohang University of Science and Technology, 77 Cheongam-ro, Nam-gu, Gyeongsangbuk-do, Pohang, 37673, South Korea
| | - Yoo-mi Choi
- Department of Convergence IT Engineering, Pohang University of Science and Technology, 77 Cheongam-ro, Nam-gu, Gyeongsangbuk-do, Pohang, 37673, South Korea
| | - In-Ho Jeon
- Department of Orthopaedic Surgery, Asan Medical Center, College of Medicine, University of Ulsan, 86 Asanbyeongwon-gil, Songpa-gu, Seoul, 05505, South Korea
| | - Homan Kang
- Gordon Center for Medical Imaging, Department of Radiology, Massachusetts General Hospital & Harvard Medical School, 149 13th Street, Boston, MA, 02114, USA
| | - Jinah Jang
- Department of Mechanical Engineering, Pohang University of Science and Technology, 77 Cheongam-ro, Nam-gu, Gyeongsangbuk-do, Pohang, 37673, South Korea
- Institute for Convergence Research and Education in Advanced Technology, Yonsei University, 50 Yonsei-ro, Seodaemun-gu, Seoul, 03722, South Korea
- Department of Convergence IT Engineering, Pohang University of Science and Technology, 77 Cheongam-ro, Nam-gu, Gyeongsangbuk-do, Pohang, 37673, South Korea
- School of Interdisciplinary Bioscience and Bioengineering, Pohang University of Science and Technology, 77 Cheongam-ro, Nam-gu, Gyeongsangbuk-do, Pohang, 37673, South Korea
| | - Hak Soo Choi
- Gordon Center for Medical Imaging, Department of Radiology, Massachusetts General Hospital & Harvard Medical School, 149 13th Street, Boston, MA, 02114, USA
- Corresponding author.
| | - Dong-Woo Cho
- Department of Mechanical Engineering, Pohang University of Science and Technology, 77 Cheongam-ro, Nam-gu, Gyeongsangbuk-do, Pohang, 37673, South Korea
- Institute for Convergence Research and Education in Advanced Technology, Yonsei University, 50 Yonsei-ro, Seodaemun-gu, Seoul, 03722, South Korea
- Corresponding author. Department of Mechanical Engineering, Pohang University of Science and Technology, 77 Cheongam-ro, Nam-gu, Pohang, 37673, Kyungbuk, South Korea.
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14
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The Role of Stem Cells Derived From the Mesenchyme of the Umbilical Cord in Reducing Immunosuppressive Drug Doses Used in Allogenic Transplantations. Ann Plast Surg 2022; 89:684-693. [DOI: 10.1097/sap.0000000000003314] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/24/2022]
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15
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Chen H, Wen X, Liu S, Sun T, Song H, Wang F, Xu J, Zhang Y, Zhao Y, Yu J, Sun L. Dissecting Heterogeneity Reveals a Unique BAMBI high MFGE8 high Subpopulation of Human UC-MSCs. ADVANCED SCIENCE (WEINHEIM, BADEN-WURTTEMBERG, GERMANY) 2022; 10:e2202510. [PMID: 36373720 PMCID: PMC9811468 DOI: 10.1002/advs.202202510] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/29/2022] [Revised: 10/12/2022] [Indexed: 06/16/2023]
Abstract
Mixed human umbilical cord-derived mesenchymal stem cells (UC-MSCs) are widely applied in clinical trials to treat various diseases due to their multipotent differentiation potential and immune regulatory activities. However, the lack of a clear understanding of their heterogeneity hampers their application to precisely treat diseases. Moreover, few studies have experimentally authenticated the functions of so-called UC-MSC subpopulations classified from scRNA-seq samples. Here, this work draws a large-scale single-cell transcriptomic atlas and identified three clusters (C1, C2, and C3), representing the primed, intermediate, and stem statuses individually. The C1 and C3 clusters feature higher expression of cytokines and stemness markers, respectively. Surprisingly, further experimental assays reveal that the BAMBIhigh MFGE8high C1 subgroup has a unique phenotype, distinct transcriptomic profile, and limited adipogenic differentiation potential but compromised immunosuppressive activity in vitro and in vivo in lupus mice. Thus, this work is helpful to clarify the nature of human UC-MSCs and to choose optimal MSC types to treat specific diseases in the future.
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Affiliation(s)
- Hongwei Chen
- Department of Rheumatology and ImmunologyThe Affiliated Drum Tower Hospital of Nanjing University Medical SchoolNanjing210008P. R. China
| | - Xin Wen
- Department of Rheumatology and ImmunologyThe Affiliated Drum Tower Hospital of Nanjing University Medical SchoolNanjing210008P. R. China
| | - Shanshan Liu
- Department of Rheumatology and ImmunologyThe Affiliated Drum Tower Hospital of Nanjing University Medical SchoolNanjing210008P. R. China
| | - Tian Sun
- Department of Rheumatology and ImmunologyThe Affiliated Drum Tower Hospital of Nanjing University Medical SchoolNanjing210008P. R. China
| | - Hua Song
- Department of Rheumatology and ImmunologyThe Affiliated Drum Tower Hospital of Nanjing University Medical SchoolNanjing210008P. R. China
| | - Fang Wang
- Department of BiochemistryInstitute of Basic Medical SciencesChinese Academy of Medical Sciences (CAMS) and School of Basic Medicine Peking Union Medical College (PUMC)Beijing100005P. R. China
| | - Jiayue Xu
- Department of BiochemistryInstitute of Basic Medical SciencesChinese Academy of Medical Sciences (CAMS) and School of Basic Medicine Peking Union Medical College (PUMC)Beijing100005P. R. China
| | - Yueyang Zhang
- School of Basic Medicine and Clinical PharmacyChina Pharmaceutical UniversityNanjing211198P. R. China
| | - Yuanjin Zhao
- Department of Rheumatology and ImmunologyThe Affiliated Drum Tower Hospital of Nanjing University Medical SchoolNanjing210008P. R. China
| | - Jia Yu
- Department of BiochemistryInstitute of Basic Medical SciencesChinese Academy of Medical Sciences (CAMS) and School of Basic Medicine Peking Union Medical College (PUMC)Beijing100005P. R. China
| | - Lingyun Sun
- Department of Rheumatology and ImmunologyThe Affiliated Drum Tower Hospital of Nanjing University Medical SchoolNanjing210008P. R. China
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16
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Kholodenko IV, Kholodenko RV, Majouga AG, Yarygin KN. Apoptotic MSCs and MSC-Derived Apoptotic Bodies as New Therapeutic Tools. Curr Issues Mol Biol 2022; 44:5153-5172. [PMID: 36354663 PMCID: PMC9688732 DOI: 10.3390/cimb44110351] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/25/2022] [Revised: 10/17/2022] [Accepted: 10/21/2022] [Indexed: 12/03/2022] Open
Abstract
Over the past two decades, mesenchymal stem cells (MSCs) have shown promising therapeutic effects both in preclinical studies (in animal models of a wide range of diseases) and in clinical trials. However, the efficacy of MSC-based therapy is not always predictable. Moreover, despite the large number of studies, the mechanisms underlying the regenerative potential of MSCs are not fully elucidated. Recently, it has been reliably established that transplanted MSCs can undergo rapid apoptosis and clearance from the recipient's body, still exhibiting therapeutic effects, especially those associated with their immunosuppressive/immunomodulating properties. The mechanisms underlying these effects can be mediated by the efferocytosis of apoptotic MSCs by host phagocytic cells. In this concise review, we briefly describe three types of MSC-generated extracellular vesicles, through which their therapeutic functions can potentially be carried out; we focused on reviewing recent data on apoptotic MSCs and MSC-derived apoptotic bodies (MSC-ApoBDs), their functions, and the mechanisms of their therapeutic effects.
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Affiliation(s)
- Irina V. Kholodenko
- Laboratory of Cell Biology, Orekhovich Institute of Biomedical Chemistry, 119121 Moscow, Russia
| | - Roman V. Kholodenko
- Laboratory of Molecular Immunology, Shemyakin–Ovchinnikov Institute of Bioorganic Chemistry of the Russian Academy of Sciences, 117997 Moscow, Russia
| | - Alexander G. Majouga
- Faculty of Chemical and Pharmaceutical Technologies and Biomedical Products, Mendeleev University of Chemical Technology of Russia, 125047 Moscow, Russia
| | - Konstantin N. Yarygin
- Laboratory of Cell Biology, Orekhovich Institute of Biomedical Chemistry, 119121 Moscow, Russia
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17
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Shi C, Pan L, Hu Z. Experimental and clinical progress of in utero hematopoietic cell transplantation therapy for congenital disorders. Front Pharmacol 2022; 13:851375. [PMID: 36120324 PMCID: PMC9478511 DOI: 10.3389/fphar.2022.851375] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/09/2022] [Accepted: 08/08/2022] [Indexed: 11/13/2022] Open
Abstract
In utero hematopoietic cell transplantation (IUHCT) is considered a potentially efficient therapeutic approach with relatively few side effects, compared to adult hematopoietic cell transplantation, for various hematological genetic disorders. The principle of IUHCT has been extensively studied in rodent models and in some large animals with close evolutionary similarities to human beings. However, IUHCT has only been used to rebuild human T cell immunity in certain patients with inherent immunodeficiencies. This review will first summarize the animal models utilized for IUHCT investigations and describe the associated outcomes. Recent advances and potential barriers for successful IUHCT are discussed, followed by possible strategies to overcome these barriers experimentally. Lastly, we will outline the progress made towards utilizing IUHCT to treat inherent disorders for patients, list out associated limitations and propose feasible means to promote the efficacy of IUHCT clinically.
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Affiliation(s)
- Chunyu Shi
- National-Local Joint Engineering Laboratory of Animal Models for Human Diseases, The First Hospital of Jilin University, Changchun, China
- Department of Gastrointestinal Colorectal and Anal Surgery, China-Japan Union Hospital of Jilin University, Changchun, China
| | - Lu Pan
- Department of Pediatric Immunology, Allergy and Rheumatology, The First Hospital of Jilin University, Changchun, China
| | - Zheng Hu
- National-Local Joint Engineering Laboratory of Animal Models for Human Diseases, The First Hospital of Jilin University, Changchun, China
- *Correspondence: Zheng Hu,
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18
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Lee DY, Choi YH, Choi JS, Eom MR, Kwon SK. Injection laryngoplasty of human adipose-derived stem cell spheroids with hyaluronic acid-based hydrogel improves the morphological and functional characteristics of geriatric larynx. Biomater Res 2022; 26:13. [PMID: 35382871 PMCID: PMC8981753 DOI: 10.1186/s40824-022-00261-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2022] [Accepted: 03/17/2022] [Indexed: 11/18/2022] Open
Abstract
Aim As the geriatric population increased, the need of treatment for laryngeal atrophy and dysfunction increased. This study was performed to evaluate the effects of injection of human adipose-derived stem cell (hASC) spheroid-loaded catechol-conjugated hyaluronic acid (HA-CA) hydrogel on therapeutic rejuvenation of the geriatric larynx. Methods Stem cell spheroids with hyaluronic acid-based hydrogel were injected into the laryngeal muscles of 18-month-old Sprague–Dawley rats. The effects of hASC spheroids were examined in the following four groups: SHAM, injected with PBS; GEL, injected with HA-CA hydrogel; MONO, injected with single hASCs in HA-CA hydrogel; and SP, injected with hASCs spheroids in HA-CA hydrogel. The rejuvenation efficacy in geriatric laryngeal muscle tissues at 12 weeks postinjection was evaluated and compared by histology, immunofluorescence staining, and functionality analysis. Results Total myofiber cross-sectional area and myofiber number/density, evaluated by detection of myosin heavy chain with antibodies against laminin and fast myosin heavy chain, were significantly higher in the SP group than in the other groups. The lamina propria of the larynx was evaluated by alcian blue staining, which showed that the HA was increased significantly in the SP group compared to the other groups. In functional analysis, the glottal gap area was significantly reduced in the SP group compared to the other groups. The phase difference in the vocal fold during vibration was also smaller in the SP group than in the other groups, but the difference did not reach statistical significance. Conclusion Injection of hASC spheroids with hyaluronic acid-based hydrogel improves the morphological and functional characteristics of geriatric larynx. Graphical abstract ![]()
Supplementary Information The online version contains supplementary material available at 10.1186/s40824-022-00261-x.
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19
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Xu Y, Gaillez MP, Zheng K, Voigt D, Cui M, Kurth T, Xiao L, Rothe R, Hauser S, Lee PW, Wieduwild R, Lin W, Bornhäuser M, Pietzsch J, Boccaccini AR, Zhang Y. A Self-Assembled Matrix System for Cell-Bioengineering Applications in Different Dimensions, Scales, and Geometries. SMALL (WEINHEIM AN DER BERGSTRASSE, GERMANY) 2022; 18:e2104758. [PMID: 35132776 DOI: 10.1002/smll.202104758] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/09/2021] [Revised: 12/30/2021] [Indexed: 06/14/2023]
Abstract
Stem cell bioengineering and therapy require different model systems and materials in different stages of development. If a chemically defined biomatrix system can fulfill most tasks, it can minimize the discrepancy among various setups. By screening biomaterials synthesized through a coacervation-mediated self-assembling mechanism, a biomatrix system optimal for 2D human mesenchymal stromal cell (hMSC) culture and osteogenesis is identified. Its utility for hMSC bioengineering is further demonstrated in coating porous bioactive glass scaffolds and nanoparticle synthesis for esiRNA delivery to knock down the SOX-9 gene with high delivery efficiency. The self-assembled injectable system is further utilized for 3D cell culture, segregated co-culture of hMSC with human umbilical vein endothelial cells (HUVEC) as an angiogenesis model, and 3D bioprinting. Most interestingly, the coating of bioactive glass with the self-assembled biomatrix not only supports the proliferation and osteogenesis of hMSC in the 3D scaffold but also induces the amorphous bioactive glass (BG) scaffold surface to form new apatite crystals resembling bone-shaped plate structures. Thus, the self-assembled biomatrix system can be utilized in various dimensions, scales, and geometries for many different bioengineering applications.
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Affiliation(s)
- Yong Xu
- B CUBE Center for Molecular Bioengineering, Technische Universität Dresden, 01307, Dresden, Germany
| | - Michelle Patino Gaillez
- B CUBE Center for Molecular Bioengineering, Technische Universität Dresden, 01307, Dresden, Germany
| | - Kai Zheng
- Institute of Biomaterials, Department of Materials Science and Engineering, University of Erlangen-Nuremberg, 91058, Erlangen, Germany
| | - Dagmar Voigt
- Institute of Botany, Faculty of Biology, Technische Universität Dresden, 01062, Dresden, Germany
| | - Meiying Cui
- B CUBE Center for Molecular Bioengineering, Technische Universität Dresden, 01307, Dresden, Germany
| | - Thomas Kurth
- Technische Universität Dresden, Center for Molecular and Cellular Bioengineering (CMCB), Technology Platform, EM Facilty, 01307, Dresden, Germany
| | - Lingfei Xiao
- Department of Spine Surgery and Musculoskeletal Tumor, Zhongnan Hospital of Wuhan University, Wuhan University, Wuhan, 430071, China
| | - Rebecca Rothe
- Helmholtz-Zentrum Dresden-Rossendorf (HZDR), Institute of Radiopharmaceutical Cancer Research Department of Radiopharmaceutical and Chemical Biology, 01328, Dresden, Germany
- Technische Universität Dresden, School of Science, Faculty of Chemistry and Food Chemistry, 01062, Dresden, Germany
| | - Sandra Hauser
- Helmholtz-Zentrum Dresden-Rossendorf (HZDR), Institute of Radiopharmaceutical Cancer Research Department of Radiopharmaceutical and Chemical Biology, 01328, Dresden, Germany
| | - Pao-Wan Lee
- B CUBE Center for Molecular Bioengineering, Technische Universität Dresden, 01307, Dresden, Germany
| | - Robert Wieduwild
- B CUBE Center for Molecular Bioengineering, Technische Universität Dresden, 01307, Dresden, Germany
| | - Weilin Lin
- B CUBE Center for Molecular Bioengineering, Technische Universität Dresden, 01307, Dresden, Germany
| | - Martin Bornhäuser
- Center for Regenerative Therapies Dresden (CRTD), Technische Universität Dresden, Fetscherstraße 105, 01307, Dresden, Germany
- University Hospital Carl Gustav Carus der Technischen Universität Dresden, Medizinische Klinik und Poliklinik I, Fetscherstraße 74, 01307, Dresden, Germany
| | - Jens Pietzsch
- Helmholtz-Zentrum Dresden-Rossendorf (HZDR), Institute of Radiopharmaceutical Cancer Research Department of Radiopharmaceutical and Chemical Biology, 01328, Dresden, Germany
- Technische Universität Dresden, School of Science, Faculty of Chemistry and Food Chemistry, 01062, Dresden, Germany
| | - Aldo R Boccaccini
- Institute of Biomaterials, Department of Materials Science and Engineering, University of Erlangen-Nuremberg, 91058, Erlangen, Germany
| | - Yixin Zhang
- B CUBE Center for Molecular Bioengineering, Technische Universität Dresden, 01307, Dresden, Germany
- Cluster of Excellence Physics of Life, Technische Universität Dresden, 01062, Dresden, Germany
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20
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Lim JY, Lee JE, Park SA, Park SI, Yon JM, Park JA, Jeun SS, Kim SJ, Lee HJ, Kim SW, Yang SH. Protective Effect of Human-Neural-Crest-Derived Nasal Turbinate Stem Cells against Amyloid-β Neurotoxicity through Inhibition of Osteopontin in a Human Cerebral Organoid Model of Alzheimer’s Disease. Cells 2022; 11:cells11061029. [PMID: 35326480 PMCID: PMC8947560 DOI: 10.3390/cells11061029] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2022] [Revised: 03/14/2022] [Accepted: 03/16/2022] [Indexed: 11/16/2022] Open
Abstract
The aim of this study was to validate the use of human brain organoids (hBOs) to investigate the therapeutic potential and mechanism of human-neural-crest-derived nasal turbinate stem cells (hNTSCs) in models of Alzheimer’s disease (AD). We generated hBOs from human induced pluripotent stem cells, investigated their characteristics according to neuronal markers and electrophysiological features, and then evaluated the protective effect of hNTSCs against amyloid-β peptide (Aβ1–42) neurotoxic activity in vitro in hBOs and in vivo in a mouse model of AD. Treatment of hBOs with Aβ1–42 induced neuronal cell death concomitant with decreased expression of neuronal markers, which was suppressed by hNTSCs cocultured under Aβ1–42 exposure. Cytokine array showed a significantly decreased level of osteopontin (OPN) in hBOs with hNTSC coculture compared with hBOs only in the presence of Aβ1–42. Silencing OPN via siRNA suppressed Aβ-induced neuronal cell death in cell culture. Notably, compared with PBS, hNTSC transplantation significantly enhanced performance on the Morris water maze, with reduced levels of OPN after transplantation in a mouse model of AD. These findings reveal that hBO models are useful to evaluate the therapeutic effect and mechanism of stem cells for application in treating AD.
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Affiliation(s)
- Jung Yeon Lim
- Department of Otolaryngology-Head and Neck Surgery, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul 06591, Korea
| | - Jung Eun Lee
- Department of Neurosurgery, St. Vincent's Hospital, College of Medicine, The Catholic University of Korea, Suwon 16247, Kyonggi-do, Korea
| | - Soon A Park
- Department of Neurosurgery, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul 06591, Korea
| | - Sang In Park
- Institute of Catholic Integrative Medicine (ICIM), Incheon St. Mary's Hospital, The Catholic University of Korea, Seoul 06591, Korea
| | - Jung-Min Yon
- Department of Otolaryngology-Head and Neck Surgery, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul 06591, Korea
| | - Jeong-Ah Park
- Department of Otolaryngology-Head and Neck Surgery, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul 06591, Korea
| | - Sin-Soo Jeun
- Department of Neurosurgery, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul 06591, Korea
| | - Seung Joon Kim
- Division of Pulmonology, Critical Care and Allergy, Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul 06591, Korea
| | - Hong Jun Lee
- College of Medicine and Medical Research Institute, Chungbuk National University, Cheongju 28644, Korea
| | - Sung Won Kim
- Department of Otolaryngology-Head and Neck Surgery, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul 06591, Korea
| | - Seung Ho Yang
- Department of Neurosurgery, St. Vincent's Hospital, College of Medicine, The Catholic University of Korea, Suwon 16247, Kyonggi-do, Korea
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Harness EM, Mohamad-Fauzi N, Murray JD. MSC therapy in livestock models. Transl Anim Sci 2022; 6:txac012. [PMID: 35356233 PMCID: PMC8962450 DOI: 10.1093/tas/txac012] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2021] [Accepted: 01/24/2022] [Indexed: 11/25/2022] Open
Abstract
Mesenchymal stem cells (MSCs) have great value as therapeutic tools in a wide array of applications in regenerative medicine. The wide repertoire of cell functions regarding tissue regeneration, immunomodulation, and antimicrobial activity makes MSC-based therapy a strong candidate for treatment options in a variety of clinical conditions and should be studied to expand the current breadth of knowledge surrounding their physiological properties and therapeutic benefits. Livestock models are an appropriate resource for testing the efficacy of MSC therapies for their use in biomedical research and can be used to improve both human health and animal agriculture. Agricultural animal models such as pigs, cattle, sheep, and goats have grown in popularity for in vivo research relative to small animal models due to their overlapping similarities in structure and function that more closely mimic the human body. Cutaneous wound healing, bone regeneration, osteoarthritis, ischemic reperfusion injury, and mastitis recovery represent a few examples of the types of disease states that may be investigated in livestock using MSC-based therapy. Although the cost of agricultural animals is greater than small animal models, the information gained using livestock as a model holds great value for human applications, and in some cases, outcompetes the weight of information gained from rodent models. With emerging fields such as exosome-based therapy, proper in vivo models will be needed for testing efficacy and translational practice, i.e., livestock models should be strongly considered as candidates. The potential for capitalizing on areas that have crossover benefits for both agricultural economic gain and improved health of the animals while minimizing the gap between translational research and clinical practice are what make livestock great choices for experimental MSC models.
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Affiliation(s)
- E M Harness
- Department of Animal Science, University of California, Davis, One Shields Ave, Davis, CA, USA
| | - N Mohamad-Fauzi
- Institute of Biological Sciences, Faculty of Science
- Institute of Ocean and Earth Sciences, Institute for Advanced Studies, Universiti Malaya, Kuala Lumpur, MALAYSIA
| | - J D Murray
- Department of Animal Science, University of California, Davis, One Shields Ave, Davis, CA, USA
- Department of Population Health and Reproduction, University of California, Davis, One Shields Ave, Davis, CA, USA
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Wang DH, Wu XM, Chen JS, Cai ZG, An JH, Zhang MY, Li Y, Li FP, Hou R, Liu YL. Isolation and characterization mesenchymal stem cells from red panda ( Ailurus fulgens styani) endometrium. CONSERVATION PHYSIOLOGY 2022; 10:coac004. [PMID: 35211318 PMCID: PMC8862722 DOI: 10.1093/conphys/coac004] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 04/25/2021] [Revised: 08/30/2021] [Accepted: 02/07/2022] [Indexed: 06/14/2023]
Abstract
Endometrial mesenchymal stem cells (eMSCs) are undifferentiated endometrial cells with self-renewal, multidirectional differentiation and high proliferation potential. Nowadays, eMSCs have been found in a few species, but it has never been reported in endangered wild animals, especially the red panda. In this study, we successfully isolated and characterized the eMSCs derived from red panda. Red panda eMSCs were fibroblast-like, had a strong proliferative potential and a stable chromosome number. Pluripotency genes including Klf4, Sox2 and Thy1 were highly expressed in eMSCs. Besides, cultured eMSCs were positive for MSC markers CD44, CD49f and CD105 and negative for endothelial cell marker CD31 and haematopoietic cell marker CD34. Moreover, no reference RNA-seq was used to analyse the eMSCs transcriptional expression profile and key pathways. Compared with skin fibroblast cell group, 9104 differentially expressed genes (DEGs) were identified, among which are 5034 genes upregulated, 4070 genes downregulated and the top 20 enrichment pathways of DEGs in Gene Ontology (GO) and the Kyoto Encyclopedia of Genes Genomes (KEGG) mainly associated with G-protein coupled receptor signalling pathway, carbohydrate derivative binding, nucleoside binding, ribosome biogenesis, cell cycle, DNA replication, Ras signalling pathway and purine metabolism. Among the DEGs, some representative genes about promoting MSCs differentiation and proliferation were upregulated and promoting fibroblasts proliferation were downregulated in eMSCs group. Red panda eMSCs also had multiple differentiation ability and could differentiate into adipocytes, chondrocytes and hepatocytes. In conclusion, we, for the first time, isolated and characterized the red panda eMSCs with ability of multiplication and multilineage differentiation in vitro. The new multipotential stem cell could be beneficial not only for the germ plasm resources conservation of red panda, but also for basic or pre-clinical studies in the future.
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Affiliation(s)
- Dong-Hui Wang
- Chengdu Research Base of Giant Panda Breeding, 1375 Panda Road, Northern Suburb, Chengdu, 610081, Sichuan Province, China
- Sichuan Key Laboratory of Conservation Biology for Endangered Wildlife, 1375 Panda Road, Northern Suburb, Chengdu, 610081, Sichuan Province, China
- Sichuan Academy of Giant Panda, 1375 Panda Road, Northern Suburb, Chengdu, 610081, Sichuan Province, China
| | - Xue-Mei Wu
- Sichuan Key Laboratory of Conservation Biology for Endangered Wildlife, 1375 Panda Road, Northern Suburb, Chengdu, 610081, Sichuan Province, China
| | - Jia-Song Chen
- Chengdu Research Base of Giant Panda Breeding, 1375 Panda Road, Northern Suburb, Chengdu, 610081, Sichuan Province, China
- Sichuan Key Laboratory of Conservation Biology for Endangered Wildlife, 1375 Panda Road, Northern Suburb, Chengdu, 610081, Sichuan Province, China
- Sichuan Academy of Giant Panda, 1375 Panda Road, Northern Suburb, Chengdu, 610081, Sichuan Province, China
| | - Zhi-Gang Cai
- Chengdu Research Base of Giant Panda Breeding, 1375 Panda Road, Northern Suburb, Chengdu, 610081, Sichuan Province, China
- Sichuan Key Laboratory of Conservation Biology for Endangered Wildlife, 1375 Panda Road, Northern Suburb, Chengdu, 610081, Sichuan Province, China
- Sichuan Academy of Giant Panda, 1375 Panda Road, Northern Suburb, Chengdu, 610081, Sichuan Province, China
| | - Jun-Hui An
- Chengdu Research Base of Giant Panda Breeding, 1375 Panda Road, Northern Suburb, Chengdu, 610081, Sichuan Province, China
- Sichuan Key Laboratory of Conservation Biology for Endangered Wildlife, 1375 Panda Road, Northern Suburb, Chengdu, 610081, Sichuan Province, China
- Sichuan Academy of Giant Panda, 1375 Panda Road, Northern Suburb, Chengdu, 610081, Sichuan Province, China
| | - Ming-Yue Zhang
- Chengdu Research Base of Giant Panda Breeding, 1375 Panda Road, Northern Suburb, Chengdu, 610081, Sichuan Province, China
- Sichuan Key Laboratory of Conservation Biology for Endangered Wildlife, 1375 Panda Road, Northern Suburb, Chengdu, 610081, Sichuan Province, China
- Sichuan Academy of Giant Panda, 1375 Panda Road, Northern Suburb, Chengdu, 610081, Sichuan Province, China
| | - Yuan Li
- Sichuan Key Laboratory of Conservation Biology for Endangered Wildlife, 1375 Panda Road, Northern Suburb, Chengdu, 610081, Sichuan Province, China
| | - Fei-Ping Li
- Chengdu Research Base of Giant Panda Breeding, 1375 Panda Road, Northern Suburb, Chengdu, 610081, Sichuan Province, China
- Sichuan Key Laboratory of Conservation Biology for Endangered Wildlife, 1375 Panda Road, Northern Suburb, Chengdu, 610081, Sichuan Province, China
- Sichuan Academy of Giant Panda, 1375 Panda Road, Northern Suburb, Chengdu, 610081, Sichuan Province, China
| | - Rong Hou
- Chengdu Research Base of Giant Panda Breeding, 1375 Panda Road, Northern Suburb, Chengdu, 610081, Sichuan Province, China
- Sichuan Key Laboratory of Conservation Biology for Endangered Wildlife, 1375 Panda Road, Northern Suburb, Chengdu, 610081, Sichuan Province, China
- Sichuan Academy of Giant Panda, 1375 Panda Road, Northern Suburb, Chengdu, 610081, Sichuan Province, China
| | - Yu-Liang Liu
- Chengdu Research Base of Giant Panda Breeding, 1375 Panda Road, Northern Suburb, Chengdu, 610081, Sichuan Province, China
- Sichuan Key Laboratory of Conservation Biology for Endangered Wildlife, 1375 Panda Road, Northern Suburb, Chengdu, 610081, Sichuan Province, China
- Sichuan Academy of Giant Panda, 1375 Panda Road, Northern Suburb, Chengdu, 610081, Sichuan Province, China
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24
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Stokes SC, Theodorou CM, Jackson JE, Pivetti C, Kumar P, Yamashiro KJ, Paxton ZJ, Reynaga L, Hyllen A, Wang A, Farmer DL. Long-term safety evaluation of placental mesenchymal stromal cells for in utero repair of myelomeningocele in a novel ovine model. J Pediatr Surg 2022; 57:18-25. [PMID: 34657738 PMCID: PMC9415987 DOI: 10.1016/j.jpedsurg.2021.09.021] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/23/2021] [Accepted: 09/08/2021] [Indexed: 01/03/2023]
Abstract
PURPOSE Augmentation of in utero myelomeningocele repair with human placental mesenchymal stromal cells seeded onto extracellular matrix (PMSC-ECM) improves motor outcomes in an ovine myelomeningocele model. This study evaluated the safety of PMSC-ECM application directly onto the fetal spinal cord in preparation for a clinical trial. METHODS Laminectomy of L5-L6 with PMSC-ECM placement directly onto the spinal cord was performed in five fetal lambs at gestational age (GA) 100-106 days. Lambs and ewes were monitored for three months following delivery. Lambs underwent magnetic resonance imaging (MRI) of the brain and spine at birth and at three months. All organs from lambs and uteri from ewes underwent histologic evaluation. Lamb spinal cords and brains and ewe placentas were evaluated for persistence of PMSCs by polymerase chain reaction for presence of human DNA. RESULTS MRIs demonstrated no evidence of abnormal tissue growth or spinal cord tethering. Histological analysis demonstrated no evidence of abnormal tissue growth or treatment related adverse effects. No human DNA was identified in evaluated tissues. CONCLUSION There was no evidence of abnormal tissue growth or PMSC persistence at three months following in utero application of PMSC-ECM to the spinal cord. This supports proceeding with clinical trials of PMSC-ECM for in utero myelomeningocele repair. LEVEL OF EVIDENCE N/A TYPE OF STUDY: Basic science.
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Affiliation(s)
- Sarah C Stokes
- Division of Pediatric General, Thoracic and Fetal Surgery, Department of Surgery, University of California Davis Medical Center, 2335 Stockton Blvd, Room 5107, Sacramento, CA 95817, USA.
| | - Christina M Theodorou
- Division of Pediatric General, Thoracic, and Fetal Surgery, Department of Surgery, University of California Davis Medical Center, Sacramento, CA 95817, USA
| | - Jordan E Jackson
- Division of Pediatric General, Thoracic, and Fetal Surgery, Department of Surgery, University of California Davis Medical Center, Sacramento, CA 95817, USA
| | - Christopher Pivetti
- Surgical Bioengineering Laboratory, University of California Davis, Sacramento, CA 95817, USA
| | - Priyadarsini Kumar
- Surgical Bioengineering Laboratory, University of California Davis, Sacramento, CA 95817, USA
| | - Kaeli J Yamashiro
- Division of Pediatric General, Thoracic, and Fetal Surgery, Department of Surgery, University of California Davis Medical Center, Sacramento, CA 95817, USA
| | - Zachary J Paxton
- Surgical Bioengineering Laboratory, University of California Davis, Sacramento, CA 95817, USA
| | - Lizette Reynaga
- Surgical Bioengineering Laboratory, University of California Davis, Sacramento, CA 95817, USA
| | - Alicia Hyllen
- Surgical Bioengineering Laboratory, University of California Davis, Sacramento, CA 95817, USA
| | - Aijun Wang
- Surgical Bioengineering Laboratory, University of California Davis, Sacramento, CA 95817, USA.,Shriners Hospital for Children Northern California, 3425 Stockton Blvd, Sacramento, CA 95817, USA
| | - Diana L Farmer
- Division of Pediatric General, Thoracic, and Fetal Surgery, Department of Surgery, University of California Davis Medical Center, Sacramento, CA 95817, USA.,Surgical Bioengineering Laboratory, University of California Davis, Sacramento, CA 95817, USA.,Shriners Hospital for Children Northern California, 3425 Stockton Blvd, Sacramento, CA 95817, USA
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25
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Marofi F, Alexandrovna KI, Margiana R, Bahramali M, Suksatan W, Abdelbasset WK, Chupradit S, Nasimi M, Maashi MS. MSCs and their exosomes: a rapidly evolving approach in the context of cutaneous wounds therapy. Stem Cell Res Ther 2021; 12:597. [PMID: 34863308 PMCID: PMC8642895 DOI: 10.1186/s13287-021-02662-6] [Citation(s) in RCA: 39] [Impact Index Per Article: 9.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/15/2021] [Accepted: 10/14/2021] [Indexed: 12/18/2022] Open
Abstract
Currently, mesenchymal stem/stromal stem cell (MSC) therapy has become a promising option for accelerating cutaneous wound healing. In vivo reports have outlined the robust competences of MSCs to offer a solid milieu by inhibition of inflammatory reactions, which in turn, enables skin regeneration. Further, due to their great potential to stimulate angiogenesis and also facilitate matrix remodeling, MSCs hold substantial potential as future therapeutic strategies in this context. The MSCs-induced wound healing is thought to mainly rely on the secretion of a myriad of paracrine factors in addition to their direct differentiation to skin-resident cells. Besides, MSCs-derived exosomes as nanoscale and closed membrane vesicles have recently been suggested as an effective and cell-free approach to support skin regeneration, circumventing the concerns respecting direct application of MSCs. The MSCs-derived exosomes comprise molecular components including lipid, proteins, DNA, microRNA, and also mRNA, which target molecular pathways and also biological activities in recipient cells (e.g., endothelial cell, keratinocyte, and fibroblast). The secreted exosome modifies macrophage activation, stimulates angiogenesis, and instigates keratinocytes and dermal fibroblast proliferations as well as migrations concurrently regulate inherent potential of myofibroblast for adjustment of turnover of the ECM. In the present review, we will focus on the recent findings concerning the application of MSCs and their derivative exosome to support wound healing and skin regeneration, with special focus on last decade in vivo reports.
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Affiliation(s)
- Faroogh Marofi
- Immunology Research Center (IRC), Tabriz University of Medical Sciences, Tabriz, Iran
| | | | - Ria Margiana
- Department of Anatomy, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia
- Master’s Programme Biomedical Sciences, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia
| | - Mahta Bahramali
- Biotechnology Department, University of Tehran, Tehran, Iran
| | - Wanich Suksatan
- Faculty of Nursing, HRH Princess Chulabhorn College of Medical Science, Chulabhorn Royal Academy, Bangkok, 10210 Thailand
| | - Walid Kamal Abdelbasset
- Department of Health and Rehabilitation Sciences, College of Applied Medical Sciences, Prince Sattam Bin Abdulaziz University, Al Kharj, Saudi Arabia
- Department of Physical Therapy, Kasr Al-Aini Hospital, Cairo University, Giza, Egypt
| | - Supat Chupradit
- Department of Occupational Therapy, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai, 50200 Thailand
| | | | - Marwah Suliman Maashi
- Stem Cells and Regenerative Medicine Unit at King Fahad Medical Research Centre, Jeddah, Saudi Arabia
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Götherström C, David AL, Walther-Jallow L, Åström E, Westgren M. Mesenchymal Stem Cell Therapy for Osteogenesis Imperfecta. Clin Obstet Gynecol 2021; 64:898-903. [PMID: 34510048 DOI: 10.1097/grf.0000000000000656] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
The aim of this study was to provide a brief overview on the background and rationale on treating fetuses and children suffering from osteogenesis imperfecta (OI) with mesenchymal stem cells (MSCs). MSCs ability to migrate, engraft, and differentiate into bone cells and to act via paracrine effects on the recipient's tissues makes these cells promising candidates as a clinical therapy for OI. Animal work and limited clinical studies in humans support the use of MSC in treating OI. Off-the-shelf MSC have a good safety profile and exhibit multilineage differentiation potential and a low immunogenic profile and thereby may enable this potential therapy to become widely available. MSC transplantation before and after birth to treat OI is an experimental therapy that is currently tested in the international multicentre phase I/II clinical trial BOOSTB4 that aims to assess the safety and efficacy of fetal MSC transplantation for the treatment of severe types of OI.
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Affiliation(s)
| | - Anna L David
- Elizabeth Garrett Anderson Institute for Women's Health, University College London, London, United Kingdom
| | | | - Eva Åström
- Woman and Child Health, Karolinska Institutet
- Department of Pediatric Neurology, Astrid Lindgren Children's Hospital at Karolinska University Hospital, Stockholm, Sweden
| | - Magnus Westgren
- Departments of Clinical Science, Intervention and Technology (CLINTEC)
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27
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Ma J, Zhan H, Li W, Zhang L, Yun F, Wu R, Lin J, Li Y. Recent trends in therapeutic strategies for repairing endometrial tissue in intrauterine adhesion. Biomater Res 2021; 25:40. [PMID: 34819167 PMCID: PMC8611984 DOI: 10.1186/s40824-021-00242-6] [Citation(s) in RCA: 74] [Impact Index Per Article: 18.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/26/2021] [Accepted: 10/31/2021] [Indexed: 12/25/2022] Open
Abstract
Intrauterine adhesion (IUA) is a common gynaecological disease that develops from infection or trauma. IUA disease may seriously affect the physical and mental health of women of childbearing age, which may lead to symptoms such as hypomenorrhea or infertility. Presently, hysteroscopic transcervical resection of adhesion (TCRA) is the principal therapy for IUAs, although its function in preventing the recurrence of adhesion and preserving fertility is limited. Pharmaceuticals such as hormones and vasoactive agents and the placement of nondegradable stents are the most common postoperative adjuvant therapy methods. However, the repair of injured endometrium is relatively restricted due to the different anatomical structures of the endometrium. Recently, the treatment outcome of IUAs has improved with the advancement of hysteroscopic techniques. In particular, the application of bioactive scaffolds combined with tissue engineering technology has proven to have high therapeutic potential or endometrial repair in IUA treatment. Herein, this review has summarized past therapeutic strategies, including postoperative adjuvant therapy, cell or therapeutic molecular delivery therapy methods and bioactive scaffold-based tissue engineering methods. Therefore, this review presented the recent therapeutic strategies for repairing endometrium treatment and pointed out the issues of clinical concern to provide alternative methods for the management of IUAs.
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Affiliation(s)
- Junyan Ma
- Zhejiang Provincial Key Laboratory for Precision Diagnosis & Treatment of Major Gynecological Diseases, Hangzhou, 310006, Zhejiang Province, China
| | - Hong Zhan
- Department of Gynecology and Obstetrics, Women' s Hospital, Zhejiang University School of Medicine, Hangzhou, 310006, Zhejiang Province, China
| | - Wen Li
- Department of Gynecology and Obstetrics, Women' s Hospital, Zhejiang University School of Medicine, Hangzhou, 310006, Zhejiang Province, China
| | - Liqi Zhang
- Department of Gynecology and Obstetrics, Women' s Hospital, Zhejiang University School of Medicine, Hangzhou, 310006, Zhejiang Province, China
| | - Feng Yun
- Department of Gynecology and Obstetrics, Women' s Hospital, Zhejiang University School of Medicine, Hangzhou, 310006, Zhejiang Province, China
| | - Ruijin Wu
- Department of Gynecology and Obstetrics, Women' s Hospital, Zhejiang University School of Medicine, Hangzhou, 310006, Zhejiang Province, China.
| | - Jun Lin
- Department of Gynecology and Obstetrics, Women' s Hospital, Zhejiang University School of Medicine, Hangzhou, 310006, Zhejiang Province, China.
| | - Yangyang Li
- Zhejiang Provincial Key Laboratory for Precision Diagnosis & Treatment of Major Gynecological Diseases, Hangzhou, 310006, Zhejiang Province, China.
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Oelze B, Elger K, Schadzek P, Burmeister L, Hamm A, Laggies S, Seiffart V, Gross G, Hoffmann A. The inflammatory signalling mediator TAK1 mediates lymphocyte recruitment to lipopolysaccharide-activated murine mesenchymal stem cells through interleukin-6. Mol Cell Biochem 2021; 476:3655-3670. [PMID: 34052945 PMCID: PMC8382631 DOI: 10.1007/s11010-021-04180-8] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2020] [Accepted: 05/12/2021] [Indexed: 10/29/2022]
Abstract
As a response to pro-inflammatory signals mesenchymal stem cells (MSCs) secrete agents and factors leading to lymphocyte recruitment, counteracting inflammation, and stimulating immunosuppression. On a molecular level, the signalling mediator TGF-β-activated kinase 1 (TAK1) is activated by many pro-inflammatory signals, plays a critical role in inflammation and regulates innate and adaptive immune responses as well. While the role of TAK1 as a signalling factor promoting inflammation is well documented, we also considered a role for TAK1 in anti-inflammatory actions exerted by activated MSCs. We, therefore, investigated the capacity of lipopolysaccharide (LPS)-treated murine MSCs with lentivirally modulated TAK1 expression levels to recruit lymphocytes. TAK1 downregulated by lentiviral vectors expressing TAK1 shRNA in murine MSCs interfered with the capacity of murine MSCs to chemoattract lymphocytes, indeed. Analysing a pool of 84 secreted factors we found that among 26 secreted cytokines/factors TAK1 regulated expression of one cytokine in LPS-activated murine MSCs in particular: interleukin-6 (IL-6). IL-6 in LPS-treated MSCs was responsible for lymphocyte recruitment as substantiated by neutralizing antibodies. Our studies, therefore, suggest that in LPS-treated murine MSCs the inflammatory signalling mediator TAK1 may exert anti-inflammatory properties via IL-6.
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Affiliation(s)
- Beatrice Oelze
- Helmholtz Centre for Infection Research (HZI), Inhoffenstr. 7, 38124, Braunschweig, Germany
| | - Kirsten Elger
- Hannover Medical School, Department of Orthopaedic Surgery, Graded Implants and Regenerative Strategies OE 8893, Stadtfelddamm 34, 30625, Hannover, Germany
- Hannover Medical School, Lower Saxony Centre for Biomedical Engineering, Implant Research and Development (NIFE), Stadtfelddamm 34, 30625, Hannover, Germany
| | - Patrik Schadzek
- Hannover Medical School, Department of Orthopaedic Surgery, Graded Implants and Regenerative Strategies OE 8893, Stadtfelddamm 34, 30625, Hannover, Germany
- Hannover Medical School, Lower Saxony Centre for Biomedical Engineering, Implant Research and Development (NIFE), Stadtfelddamm 34, 30625, Hannover, Germany
| | - Laura Burmeister
- Hannover Medical School, Department of Orthopaedic Surgery, Graded Implants and Regenerative Strategies OE 8893, Stadtfelddamm 34, 30625, Hannover, Germany
- Hannover Medical School, Lower Saxony Centre for Biomedical Engineering, Implant Research and Development (NIFE), Stadtfelddamm 34, 30625, Hannover, Germany
| | - Anika Hamm
- Hannover Medical School, Department of Orthopaedic Surgery, Graded Implants and Regenerative Strategies OE 8893, Stadtfelddamm 34, 30625, Hannover, Germany
- Hannover Medical School, Lower Saxony Centre for Biomedical Engineering, Implant Research and Development (NIFE), Stadtfelddamm 34, 30625, Hannover, Germany
| | - Sandra Laggies
- Helmholtz Centre for Infection Research (HZI), Inhoffenstr. 7, 38124, Braunschweig, Germany
| | - Virginia Seiffart
- Helmholtz Centre for Infection Research (HZI), Inhoffenstr. 7, 38124, Braunschweig, Germany
| | - Gerhard Gross
- Helmholtz Centre for Infection Research (HZI), Inhoffenstr. 7, 38124, Braunschweig, Germany
| | - Andrea Hoffmann
- Helmholtz Centre for Infection Research (HZI), Inhoffenstr. 7, 38124, Braunschweig, Germany.
- Hannover Medical School, Department of Orthopaedic Surgery, Graded Implants and Regenerative Strategies OE 8893, Stadtfelddamm 34, 30625, Hannover, Germany.
- Hannover Medical School, Lower Saxony Centre for Biomedical Engineering, Implant Research and Development (NIFE), Stadtfelddamm 34, 30625, Hannover, Germany.
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29
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Mesenchymal stem cells from biology to therapy. Emerg Top Life Sci 2021; 5:539-548. [PMID: 34355761 PMCID: PMC8639183 DOI: 10.1042/etls20200303] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/05/2021] [Revised: 05/30/2021] [Accepted: 07/21/2021] [Indexed: 01/07/2023]
Abstract
Mesenchymal stem cells are as fascinating as they are enigmatic. They appear capable of performing a wide array of functions that cross skeletal biology, immunology and haematology. As therapeutics, mesenchymal stem cells or even just their secreted products may be used to regenerate tissue lost through injury or disease and suppress damaging immune reactions. However, these cells lack unique markers and are hard to identify and isolate as pure cell populations. They are often grown in laboratories using basic and undefined culture conditions. We cannot even agree on their name. While mesenchymal stem cells may lack the developmental understanding and defined differentiation hierarchies of their more illustrious stem cell cousins, they offer a compelling scientific challenge. In depth understanding of mesenchymal stem cell biology will enable us to exploit fully one of the most clinically valuable cell sources.
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30
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Lin S, Chen Q, Zhang L, Ge S, Luo Y, He W, Xu C, Zeng M. Overexpression of HOXB4 Promotes Protection of Bone Marrow Mesenchymal Stem Cells Against Lipopolysaccharide-Induced Acute Lung Injury Partially Through the Activation of Wnt/β-Catenin Signaling. J Inflamm Res 2021; 14:3637-3649. [PMID: 34349541 PMCID: PMC8326777 DOI: 10.2147/jir.s319416] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2021] [Accepted: 07/19/2021] [Indexed: 12/12/2022] Open
Abstract
PURPOSE Pulmonary vascular endothelial cell (EC) injury is recognized as one of the pathological factors of acute lung injury/acute respiratory distress syndrome (ALI/ARDS). Bone marrow mesenchymal stem cell (BMSC)-based cytotherapy has attracted substantial attention over recent years as a promising therapeutic approach for ALI/ARDS; however, its use remains limited due to inconsistent efficacy. Currently, gene modification techniques are widely applied to MSCs. In the present study, we aimed to investigate the effect of BMSCs overexpressing Homeobox B4 (HOXB4) on lipopolysaccharide (LPS)-induced EC injury. METHODS We used LPS to induce EC injury and established EC-BMSC coculture system using transwell chambers. The effect of BMSCs on ECs was explored by detecting EC proliferation, apoptosis, migration, tube formation, and permeability, and determining whether the Wnt/β-catenin pathway is involved in the regulatory mechanism using XAV-939, inhibitor of Wnt/ β-catenin. RESULTS As compared to BMSCWT, BMSCHOXB4 coculture promoted EC proliferation, migration, and tube formation after LPS stimulation and attenuated LPS-induced EC apoptosis and vascular permeability. Mechanistically, BMSCHOXB4 coculture prevented LPS-induced EC injury by activating the Wnt/β-catenin pathway, which is partially reversible by XAV-939. When cocultured with BMSCHOXB4, pro-inflammatory factors were dramatically decreased and anti-inflammatory factors were greatly increased in the EC medium compared to those in the LPS group (P<0.05). Additionally, when compared to BMSCWT coculture, the BMSCHOXB4 coculture showed an enhanced modulation of IL-6, TNF-α, and IL-10, but there was no statistically significant effect on IL-1β and IL-4. CONCLUSION Coculturing of BMSCHOXB4 prevented LPS-induced EC injury by reversing the inactivation of the Wnt/β-catenin signaling pathway. An in vivo study remains warranted to ascertain whether engraftment of BMSCHOXB4 can be an attractive strategy for the treatment of ALI/ARDS.
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Affiliation(s)
- Shan Lin
- Department of Medical Intensive Care Unit, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, 510080, People’s Republic of China
- Institute of Pulmonary Diseases, Sun Yat-sen University, Guangzhou, Guangdong, People’s Republic of China
| | - Qingui Chen
- Department of Medical Intensive Care Unit, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, 510080, People’s Republic of China
- Institute of Pulmonary Diseases, Sun Yat-sen University, Guangzhou, Guangdong, People’s Republic of China
| | - Lishan Zhang
- Department of Medical Intensive Care Unit, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, 510080, People’s Republic of China
- Institute of Pulmonary Diseases, Sun Yat-sen University, Guangzhou, Guangdong, People’s Republic of China
| | - Shanhui Ge
- Department of Medical Intensive Care Unit, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, 510080, People’s Republic of China
- Institute of Pulmonary Diseases, Sun Yat-sen University, Guangzhou, Guangdong, People’s Republic of China
| | - Yuling Luo
- Department of Medical Intensive Care Unit, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, 510080, People’s Republic of China
- Institute of Pulmonary Diseases, Sun Yat-sen University, Guangzhou, Guangdong, People’s Republic of China
| | - Wanmei He
- Department of Medical Intensive Care Unit, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, 510080, People’s Republic of China
- Institute of Pulmonary Diseases, Sun Yat-sen University, Guangzhou, Guangdong, People’s Republic of China
| | - Caixia Xu
- Research Center of Translational Medicine, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, People’s Republic of China
| | - Mian Zeng
- Department of Medical Intensive Care Unit, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, 510080, People’s Republic of China
- Institute of Pulmonary Diseases, Sun Yat-sen University, Guangzhou, Guangdong, People’s Republic of China
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Lim JY, In Park S, Park SA, Jeon JH, Jung HY, Yon JM, Jeun SS, Lim HK, Kim SW. Potential application of human neural crest-derived nasal turbinate stem cells for the treatment of neuropathology and impaired cognition in models of Alzheimer's disease. Stem Cell Res Ther 2021; 12:402. [PMID: 34256823 PMCID: PMC8278635 DOI: 10.1186/s13287-021-02489-1] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2020] [Accepted: 07/02/2021] [Indexed: 12/21/2022] Open
Abstract
Background Stem cell transplantation is a fascinating therapeutic approach for the treatment of many neurodegenerative disorders; however, clinical trials using stem cells have not been as effective as expected based on preclinical studies. The aim of this study is to validate the hypothesis that human neural crest-derived nasal turbinate stem cells (hNTSCs) are a clinically promising therapeutic source of adult stem cells for the treatment of Alzheimer’s disease (AD). Methods hNTSCs were evaluated in comparison with human bone marrow-derived mesenchymal stem cells (hBM-MSCs) according to the effect of transplantation on AD pathology, including PET/CT neuroimaging, immune status indicated by microglial numbers and autophagic capacity, neuronal survival, and cognition, in a 5 × FAD transgenic mouse model of AD. Results We demonstrated that hNTSCs showed a high proliferative capacity and great neurogenic properties in vitro. Compared with hBM-MSC transplantation, hNTSC transplantation markedly reduced Aβ42 levels and plaque formation in the brains of the 5 × FAD transgenic AD mice on neuroimaging, concomitant with increased survival of hippocampal and cortex neurons. Moreover, hNTSCs strongly modulated immune status by reducing the number of microglia and the expression of the inflammatory cytokine IL-6 and upregulating autophagic capacity at 7 weeks after transplantation in AD models. Notably, compared with transplantation of hBM-MSCs, transplantation of hNTSCs significantly enhanced performance on the Morris water maze, with an increased level of TIMP2, which is necessary for spatial memory in young mice and neurons; this difference could be explained by the high engraftment of hNTSCs after transplantation. Conclusion The reliable evidence provided by these findings reveals a promising therapeutic effect of hNTSCs and indicates a step forward the clinical application of hNTSCs in patients with AD.
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Affiliation(s)
- Jung Yeon Lim
- Department of Otolaryngology-Head and Neck Surgery, Seoul St. Mary's Hospital, The Catholic University of Korea, 222 Banpo-Daero, Seocho-gu, Seoul, 06591, Republic of Korea.
| | - Sang In Park
- Institute of Catholic Integrative Medicine (ICIM), Incheon St. Mary's Hospital, The Catholic University of Korea, 56 Dongsu-ro, Bupyeong-gu, Incheon, 21431, Republic of Korea
| | - Soon A Park
- Department of Neurosurgery, Seoul St. Mary's Hospital, The Catholic University of Korea, 222 Banpo-Daero, Seocho-gu, Seoul, 06591, Republic of Korea
| | - Jung Ho Jeon
- Department of Otolaryngology-Head and Neck Surgery, Seoul St. Mary's Hospital, The Catholic University of Korea, 222 Banpo-Daero, Seocho-gu, Seoul, 06591, Republic of Korea
| | - Ho Yong Jung
- Institute of Catholic Integrative Medicine (ICIM), Incheon St. Mary's Hospital, The Catholic University of Korea, 56 Dongsu-ro, Bupyeong-gu, Incheon, 21431, Republic of Korea
| | - Jung-Min Yon
- Department of Otolaryngology-Head and Neck Surgery, Seoul St. Mary's Hospital, The Catholic University of Korea, 222 Banpo-Daero, Seocho-gu, Seoul, 06591, Republic of Korea
| | - Sin-Soo Jeun
- Department of Neurosurgery, Seoul St. Mary's Hospital, The Catholic University of Korea, 222 Banpo-Daero, Seocho-gu, Seoul, 06591, Republic of Korea
| | - Hyun Kook Lim
- Department of Psychiatry, Yeouido St. Mary's Hospital, The Catholic University of Korea, 63-ro 10, Yeoungdeungpo-gu, Seoul, 07345, Republic of Korea
| | - Sung Won Kim
- Department of Otolaryngology-Head and Neck Surgery, Seoul St. Mary's Hospital, The Catholic University of Korea, 222 Banpo-Daero, Seocho-gu, Seoul, 06591, Republic of Korea.
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Progress in Mesenchymal Stem Cell Therapy for Ischemic Stroke. Stem Cells Int 2021; 2021:9923566. [PMID: 34221026 PMCID: PMC8219421 DOI: 10.1155/2021/9923566] [Citation(s) in RCA: 34] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2021] [Revised: 05/27/2021] [Accepted: 06/03/2021] [Indexed: 12/12/2022] Open
Abstract
Ischemic stroke (IS) is a serious cerebrovascular disease with high morbidity and disability worldwide. Despite the great efforts that have been made, the prognosis of patients with IS remains unsatisfactory. Notably, recent studies indicated that mesenchymal stem cell (MSCs) therapy is becoming a novel research hotspot with large potential in treating multiple human diseases including IS. The current article is aimed at reviewing the progress of MSC treatment on IS. The mechanism of MSCs in the treatment of IS involved with immune regulation, neuroprotection, angiogenesis, and neural circuit reconstruction. In addition, nutritional cytokines, mitochondria, and extracellular vesicles (EVs) may be the main mediators of the therapeutic effect of MSCs. Transplantation of MSCs-derived EVs (MSCs-EVs) affords a better neuroprotective against IS when compared with transplantation of MSCs alone. MSC therapy can prolong the treatment time window of ischemic stroke, and early administration within 7 days after stroke may be the best treatment opportunity. The deliver routine consists of intraventricular, intravascular, intranasal, and intraperitoneal. Furthermore, several methods such as hypoxic preconditioning and gene technology could increase the homing and survival ability of MSCs after transplantation. In addition, MSCs combined with some drugs or physical therapy measures also show better neurological improvement. These data supported the notion that MSC therapy might be a promising therapeutic strategy for IS. And the application of new technology will promote MSC therapy of IS.
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Noncultured Minimally Processed Adipose-Derived Stem Cells Improve Radiated Fracture Healing. Ann Plast Surg 2021; 85:83-88. [PMID: 32187072 DOI: 10.1097/sap.0000000000002354] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
Abstract
Adipose-derived stem cells mitigate deleterious effects of radiation on bone and enhance radiated fracture healing by replacing damaged cells and stimulating angiogenesis. However, adipose-derived stem cell harvest and delivery techniques must be refined to comply with the US Food and Drug Administration restrictions on implantation of cultured cells into human subjects prior to clinical translation. The purpose of this study is to demonstrate the preservation of efficacy of adipose-derived stem cells to remediate the injurious effects of radiation on fracture healing utilizing a novel harvest and delivery technique that avoids the need for cell culture. Forty-four Lewis rats were divided into 4 groups: fracture control (Fx), radiated fracture control (XFx), radiated fracture treated with cultured adipose-derived stem cells (ASC), and radiated fracture treated with noncultured minimally processed adipose-derived stem cells (MP-ASC). Excluding the Fx group, all rats received a fractionated human-equivalent dose of radiation. All groups underwent mandibular osteotomy with external fixation. Following sacrifice on postoperative day 40, union rate, mineralization, and biomechanical strength were compared between groups at P < 0.05 significance. Compared with Fx controls, the XFx group demonstrated decreased union rate (100% vs 20%), bone volume fraction (P = 0.003), and ultimate load (P < 0.001). Compared with XFx controls, the MP-ASC group tripled the union rate (20% vs 60%) and demonstrated statistically significant increases in both bone volume fraction (P = 0.005) and ultimate load (P = 0.025). Compared with the MP-ASC group, the ASC group showed increased union rate (60% vs 100%) and no significant difference in bone volume fraction (P = 0.936) and ultimate load (P = 0.202). Noncultured minimally processed adipose-derived stem cells demonstrate the capacity to improve irradiated fracture healing without the need for cell proliferation in culture. Further refinement of the cell harvest and delivery techniques demonstrated in this report will enhance the ability of noncultured minimally processed adipose-derived stem cells to improve union rate and bone quality, thereby optimizing clinical translation.
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Liu B, Qiao G, Cao W, Li CH, Pan SH, Wang L, Liu Y, Ma L, Cui D. Proteomics Analyses Reveal Functional Differences between Exosomes of Mesenchymal Stem Cells Derived from The Umbilical Cord and Those Derived from The Adipose Tissue. CELL JOURNAL 2021; 23:75-84. [PMID: 33650823 PMCID: PMC7944129 DOI: 10.22074/cellj.2021.6969] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/24/2019] [Accepted: 12/11/2019] [Indexed: 11/06/2022]
Abstract
OBJECTIVE We aimed to identify the differentially expressed proteins (DEPs) and functional differences between exosomes derived from mesenchymal stem cells (MSCs) derived from umbilical cord (UC) or adipose tissue (AD). MATERIALS AND METHODS In this experimental study, the UC and AD were isolated from healthy volunteers. Then, exosomes from UC-MSCs and AD-MSCs were isolated and characterized. Next, the protein compositions of the exosomes were examined via liquid chromatography tandem mass spectrometry (LC-MS/MS), followed by evaluation of the DEPs between UC-MSC and AD-MSC-derived exosomes. Finally, functional enrichment analysis was performed. RESULTS One hundred and ninety-eight key DEPs were identified, among which, albumin (ALB), alpha-II-spectrin (SPTAN1), and Ras-related C3 botulinum toxin substrate 2 (RAC2) were the three hub proteins present at the highest levels in the protein-protein interaction network that was generated based on the shared DEPs. The DEPs were mainly enriched in gene ontology (GO) items associated with immunity, complement activation, and protein activation cascade regulation corresponding to 24 pathways, of which complement and coagulation cascades as well as platelet activation pathways were the most significant. CONCLUSION The different functions of AD- and UC-MSC exosomes in clinical applications may be related to the differences in their immunomodulatory activities.
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Affiliation(s)
- Bin Liu
- Institute of Nano Biomedicine and Engineering, Shanghai Engineering Research Center for Intelligent Diagnosis and Treatment Instrument, Department of Instrument Science and Engineering, School of Electronic Information and Electrical Engineering, Shanghai Jiao Tong University, China
- National Center for Translational Medicine, Collaborative Innovational Center for System Biology, Shanghai Jiao Tong University, China
| | - Guanglei Qiao
- Department of Oncology, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, China
| | - Wen Cao
- Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Shanghai Jiao Tong University, China
| | - C Henlu Li
- School of Laboratory Medicine and Life Science, Wenzhou Medical University, University Town, Chashan, China
| | - S Haojun Pan
- School of Biomedical Engineering, Shanghai Jiao Tong University, China
| | - Lirui Wang
- Institute of Nano Biomedicine and Engineering, Shanghai Engineering Research Center for Intelligent Diagnosis and Treatment Instrument, Department of Instrument Science and Engineering, School of Electronic Information and Electrical Engineering, Shanghai Jiao Tong University, China
- National Center for Translational Medicine, Collaborative Innovational Center for System Biology, Shanghai Jiao Tong University, China
| | - Yanlei Liu
- Institute of Nano Biomedicine and Engineering, Shanghai Engineering Research Center for Intelligent Diagnosis and Treatment Instrument, Department of Instrument Science and Engineering, School of Electronic Information and Electrical Engineering, Shanghai Jiao Tong University, China
- National Center for Translational Medicine, Collaborative Innovational Center for System Biology, Shanghai Jiao Tong University, China
| | - Lijun Ma
- Department of Oncology, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, China.
| | - Daxiang Cui
- Institute of Nano Biomedicine and Engineering, Shanghai Engineering Research Center for Intelligent Diagnosis and Treatment Instrument, Department of Instrument Science and Engineering, School of Electronic Information and Electrical Engineering, Shanghai Jiao Tong University, China.
- National Center for Translational Medicine, Collaborative Innovational Center for System Biology, Shanghai Jiao Tong University, China
- Department of Oncology, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, China
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Zhang T, Huang T, Su Y, Gao J. Mesenchymal Stem Cells‐Based Targeting Delivery System: Therapeutic Promises and Immunomodulation against Tumor. ADVANCED THERAPEUTICS 2021. [DOI: 10.1002/adtp.202100030] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Affiliation(s)
- Tianyuan Zhang
- Zhejiang Province Key Laboratory of Anti‐Cancer Drug Research College of Pharmaceutical Sciences Zhejiang University 866 Yuhangtang Rd Hangzhou 310058 China
- Dr. Li Dak Sum & Yip Yio Chin Center for Stem Cell and Regenerative Medicine Zhejiang University 866 Yuhangtang Rd Hangzhou 310058 China
| | - Ting Huang
- Zhejiang Province Key Laboratory of Anti‐Cancer Drug Research College of Pharmaceutical Sciences Zhejiang University 866 Yuhangtang Rd Hangzhou 310058 China
| | - Yuanqin Su
- Zhejiang Province Key Laboratory of Anti‐Cancer Drug Research College of Pharmaceutical Sciences Zhejiang University 866 Yuhangtang Rd Hangzhou 310058 China
| | - Jianqing Gao
- Zhejiang Province Key Laboratory of Anti‐Cancer Drug Research College of Pharmaceutical Sciences Zhejiang University 866 Yuhangtang Rd Hangzhou 310058 China
- Dr. Li Dak Sum & Yip Yio Chin Center for Stem Cell and Regenerative Medicine Zhejiang University 866 Yuhangtang Rd Hangzhou 310058 China
- Cancer Center of Zhejiang University 866 Yuhangtang Rd Hangzhou 310058 China
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Cai X, Daniels O, Cucchiarini M, Madry H. Ectopic models recapitulating morphological and functional features of articular cartilage. Ann Anat 2021; 237:151721. [PMID: 33753232 DOI: 10.1016/j.aanat.2021.151721] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/22/2021] [Revised: 02/16/2021] [Accepted: 02/17/2021] [Indexed: 10/21/2022]
Abstract
BACKGROUND Articular cartilage is an extremely specialized connective tissue which covers all diarthrodial joints. Implantation of chondrogenic cells without or with additional biomaterial scaffolds in ectopic locationsin vivo generates substitutes of cartilage with structural and functional characteristics that are used in fundamental investigations while also serving as a basis for translational studies. METHODS Literature search in Pubmed. RESULTS AND DISCUSSION This narrative review summarizes the most relevant ectopic models, among which subcutaneous, intramuscular, and kidney capsule transplantation and elaborates on implanted cells and biomaterial scaffolds and on their use to recapitulate morphological and functional features of articular cartilage. Although the absence of a physiological joint environment and biomechanical stimuli is the major limiting factor, ectopic models are an established component for articular cartilage research aiming to generate a bridge between in vitro data and the clinically more relevant translational orthotopic in vivo models when their limitations are considered.
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Affiliation(s)
- Xiaoyu Cai
- Center of Experimental Orthopaedics, Saarland University, Homburg, Germany
| | - Oliver Daniels
- Center of Experimental Orthopaedics, Saarland University, Homburg, Germany
| | - Magali Cucchiarini
- Center of Experimental Orthopaedics, Saarland University, Homburg, Germany
| | - Henning Madry
- Center of Experimental Orthopaedics, Saarland University, Homburg, Germany.
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Monaco G, El Haj AJ, Alini M, Stoddart MJ. Ex Vivo Systems to Study Chondrogenic Differentiation and Cartilage Integration. J Funct Morphol Kinesiol 2021; 6:E6. [PMID: 33466400 PMCID: PMC7838775 DOI: 10.3390/jfmk6010006] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/25/2020] [Revised: 12/18/2020] [Accepted: 12/23/2020] [Indexed: 12/21/2022] Open
Abstract
Articular cartilage injury and repair is an issue of growing importance. Although common, defects of articular cartilage present a unique clinical challenge due to its poor self-healing capacity, which is largely due to its avascular nature. There is a critical need to better study and understand cellular healing mechanisms to achieve more effective therapies for cartilage regeneration. This article aims to describe the key features of cartilage which is being modelled using tissue engineered cartilage constructs and ex vivo systems. These models have been used to investigate chondrogenic differentiation and to study the mechanisms of cartilage integration into the surrounding tissue. The review highlights the key regeneration principles of articular cartilage repair in healthy and diseased joints. Using co-culture models and novel bioreactor designs, the basis of regeneration is aligned with recent efforts for optimal therapeutic interventions.
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Affiliation(s)
- Graziana Monaco
- AO Research Institute Davos, Clavadelerstrasse 8, CH-7270 Davos Platz, Switzerland; (G.M.); (M.A.)
- School of Pharmacy & Bioengineering Research, University of Keele, Keele ST5 5BG, UK;
| | - Alicia J. El Haj
- School of Pharmacy & Bioengineering Research, University of Keele, Keele ST5 5BG, UK;
- Healthcare Technology Institute, Translational Medicine, School of Chemical Engineering, University of Birmingham, Birmingham B15 2TH, UK
| | - Mauro Alini
- AO Research Institute Davos, Clavadelerstrasse 8, CH-7270 Davos Platz, Switzerland; (G.M.); (M.A.)
| | - Martin J. Stoddart
- AO Research Institute Davos, Clavadelerstrasse 8, CH-7270 Davos Platz, Switzerland; (G.M.); (M.A.)
- School of Pharmacy & Bioengineering Research, University of Keele, Keele ST5 5BG, UK;
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38
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Zhang R, Guo T, Han Y, Huang H, Shi J, Hu J, Li H, Wang J, Saleem A, Zhou P, Lan F. Design of synthetic microenvironments to promote the maturation of human pluripotent stem cell derived cardiomyocytes. J Biomed Mater Res B Appl Biomater 2020; 109:949-960. [PMID: 33231364 DOI: 10.1002/jbm.b.34759] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2020] [Revised: 10/08/2020] [Accepted: 11/10/2020] [Indexed: 12/19/2022]
Abstract
Cardiomyocyte like cells derived from human pluripotent stem cells (hPSC-CMs) have a good application perspective in many fields such as disease modeling, drug screening and clinical treatment. However, these are severely hampered by the fact that hPSC-CMs are immature compared to adult human cardiomyocytes. Therefore, many approaches such as genetic manipulation, biochemical factors supplement, mechanical stress, electrical stimulation and three-dimensional culture have been developed to promote the maturation of hPSC-CMs. Recently, establishing in vitro synthetic artificial microenvironments based on the in vivo development program of cardiomyocytes has achieved much attention due to their inherent properties such as stiffness, plasticity, nanotopography and chemical functionality. In this review, the achievements and deficiency of reported synthetic microenvironments that mainly discussed comprehensive biological, chemical, and physical factors, as well as three-dimensional culture were mainly discussed, which have significance to improve the microenvironment design and accelerate the maturation of hPSC-CMs.
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Affiliation(s)
- Rui Zhang
- School and hospital of Stomatology, Lanzhou University, Lanzhou, China.,College of Life Sciences, Lanzhou University, Lanzhou, China
| | - Tianwei Guo
- Beijing Anzhen Hospital, Capital Medical University, Beijing, China
| | - Yu Han
- School and hospital of Stomatology, Lanzhou University, Lanzhou, China
| | - Hongxin Huang
- School and hospital of Stomatology, Lanzhou University, Lanzhou, China
| | - Jiamin Shi
- College of Life Sciences, Lanzhou University, Lanzhou, China
| | - Jiaxuan Hu
- College of Chemistry and Chemical Engineering, Lanzhou University, Lanzhou, China
| | - Hongjiao Li
- School and hospital of Stomatology, Lanzhou University, Lanzhou, China
| | - Jianlin Wang
- College of Life Sciences, Lanzhou University, Lanzhou, China
| | - Amina Saleem
- Beijing Anzhen Hospital, Capital Medical University, Beijing, China
| | - Ping Zhou
- School and hospital of Stomatology, Lanzhou University, Lanzhou, China
| | - Feng Lan
- National Center for Cardiovascular Diseases, Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
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Słomka A, Mocan T, Wang B, Nenu I, Urban SK, Gonzalez-Carmona MA, Schmidt-Wolf IGH, Lukacs-Kornek V, Strassburg CP, Spârchez Z, Kornek M. EVs as Potential New Therapeutic Tool/Target in Gastrointestinal Cancer and HCC. Cancers (Basel) 2020; 12:3019. [PMID: 33080904 PMCID: PMC7603109 DOI: 10.3390/cancers12103019] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2020] [Revised: 10/04/2020] [Accepted: 10/13/2020] [Indexed: 02/07/2023] Open
Abstract
For more than a decade, extracellular vesicles (EVs) have been in focus of science. Once thought to be an efficient way to eliminate undesirable cell content, EVs are now well-accepted as being an important alternative to cytokines and chemokines in cell-to-cell communication route. With their cargos, mainly consisting of functional proteins, lipids and nucleic acids, they can activate signalling cascades and thus change the phenotype of recipient cells at local and systemic levels. Their substantial role as modulators of various physiological and pathological processes is acknowledged. Importantly, more and more evidence arises that EVs play a pivotal role in many stages of carcinogenesis. Via EV-mediated communication, tumour cells can manipulate cells from host immune system or from the tumour microenvironment, and, ultimately, they promote tumour progression and modulate host immunity towards tumour's favour. Additionally, the role of EVs in modulating resistance to pharmacological and radiological therapy of many cancer types has become evident lately. Our understanding of EV biology and their role in cancer promotion and drug resistance has evolved considerably in recent years. In this review, we specifically discuss the current knowledge on the association between EVs and gastrointestinal (GI) and liver cancers, including their potential for diagnosis and treatment.
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Affiliation(s)
- Artur Słomka
- Department of Pathophysiology, Nicolaus Copernicus University in Toruń, Ludwik Rydygier Collegium Medicum in Bydgoszcz, 85-067 Bydgoszcz, Poland;
| | - Tudor Mocan
- Octavian Fodor Institute for Gastroenterology and Hepatology, Iuliu Haţieganu, University of Medicine and Pharmacy, 400162 Cluj-Napoca, Romania; (T.M.); (I.N.); (Z.S.)
| | - Bingduo Wang
- Department of Internal Medicine I, University Hospital of the Rheinische Friedrich-Wilhelms-University, 53127 Bonn, Germany; (B.W.); (S.K.U.); (M.G.-C.); (C.P.S.)
| | - Iuliana Nenu
- Octavian Fodor Institute for Gastroenterology and Hepatology, Iuliu Haţieganu, University of Medicine and Pharmacy, 400162 Cluj-Napoca, Romania; (T.M.); (I.N.); (Z.S.)
| | - Sabine K. Urban
- Department of Internal Medicine I, University Hospital of the Rheinische Friedrich-Wilhelms-University, 53127 Bonn, Germany; (B.W.); (S.K.U.); (M.G.-C.); (C.P.S.)
| | - Maria A. Gonzalez-Carmona
- Department of Internal Medicine I, University Hospital of the Rheinische Friedrich-Wilhelms-University, 53127 Bonn, Germany; (B.W.); (S.K.U.); (M.G.-C.); (C.P.S.)
| | - Ingo G. H. Schmidt-Wolf
- Department of Integrated Oncology, Center for Integrated Oncology (CIO), University Hospital of the Rheinische Friedrich-Wilhelms-University, 53127 Bonn, Germany;
| | - Veronika Lukacs-Kornek
- Institute of Experimental Immunology, University Hospital of the Rheinische Friedrich-Wilhelms-University, 53127 Bonn, Germany;
| | - Christian P. Strassburg
- Department of Internal Medicine I, University Hospital of the Rheinische Friedrich-Wilhelms-University, 53127 Bonn, Germany; (B.W.); (S.K.U.); (M.G.-C.); (C.P.S.)
| | - Zeno Spârchez
- Octavian Fodor Institute for Gastroenterology and Hepatology, Iuliu Haţieganu, University of Medicine and Pharmacy, 400162 Cluj-Napoca, Romania; (T.M.); (I.N.); (Z.S.)
| | - Miroslaw Kornek
- Department of Internal Medicine I, University Hospital of the Rheinische Friedrich-Wilhelms-University, 53127 Bonn, Germany; (B.W.); (S.K.U.); (M.G.-C.); (C.P.S.)
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Ribitsch I, Baptista PM, Lange-Consiglio A, Melotti L, Patruno M, Jenner F, Schnabl-Feichter E, Dutton LC, Connolly DJ, van Steenbeek FG, Dudhia J, Penning LC. Large Animal Models in Regenerative Medicine and Tissue Engineering: To Do or Not to Do. Front Bioeng Biotechnol 2020; 8:972. [PMID: 32903631 PMCID: PMC7438731 DOI: 10.3389/fbioe.2020.00972] [Citation(s) in RCA: 145] [Impact Index Per Article: 29.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/12/2020] [Accepted: 07/27/2020] [Indexed: 12/13/2022] Open
Abstract
Rapid developments in Regenerative Medicine and Tissue Engineering has witnessed an increasing drive toward clinical translation of breakthrough technologies. However, the progression of promising preclinical data to achieve successful clinical market authorisation remains a bottleneck. One hurdle for progress to the clinic is the transition from small animal research to advanced preclinical studies in large animals to test safety and efficacy of products. Notwithstanding this, to draw meaningful and reliable conclusions from animal experiments it is critical that the species and disease model of choice is relevant to answer the research question as well as the clinical problem. Selecting the most appropriate animal model requires in-depth knowledge of specific species and breeds to ascertain the adequacy of the model and outcome measures that closely mirror the clinical situation. Traditional reductionist approaches in animal experiments, which often do not sufficiently reflect the studied disease, are still the norm and can result in a disconnect in outcomes observed between animal studies and clinical trials. To address these concerns a reconsideration in approach will be required. This should include a stepwise approach using in vitro and ex vivo experiments as well as in silico modeling to minimize the need for in vivo studies for screening and early development studies, followed by large animal models which more closely resemble human disease. Naturally occurring, or spontaneous diseases in large animals remain a largely untapped resource, and given the similarities in pathophysiology to humans they not only allow for studying new treatment strategies but also disease etiology and prevention. Naturally occurring disease models, particularly for longer lived large animal species, allow for studying disorders at an age when the disease is most prevalent. As these diseases are usually also a concern in the chosen veterinary species they would be beneficiaries of newly developed therapies. Improved awareness of the progress in animal models is mutually beneficial for animals, researchers, human and veterinary patients. In this overview we describe advantages and disadvantages of various animal models including domesticated and companion animals used in regenerative medicine and tissue engineering to provide an informed choice of disease-relevant animal models.
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Affiliation(s)
- Iris Ribitsch
- Veterm, Department for Companion Animals and Horses, University Equine Hospital, University of Veterinary Medicine Vienna, Vienna, Austria
| | - Pedro M. Baptista
- Laboratory of Organ Bioengineering and Regenerative Medicine, Health Research Institute of Aragon (IIS Aragon), Zaragoza, Spain
| | - Anna Lange-Consiglio
- Department of Veterinary Medicine, Università degli Studi di Milano, Milan, Italy
| | - Luca Melotti
- Department of Comparative Biomedicine and Food Science, University of Padua, Padua, Italy
| | - Marco Patruno
- Department of Comparative Biomedicine and Food Science, University of Padua, Padua, Italy
| | - Florien Jenner
- Veterm, Department for Companion Animals and Horses, University Equine Hospital, University of Veterinary Medicine Vienna, Vienna, Austria
| | - Eva Schnabl-Feichter
- Clinical Unit of Small Animal Surgery, Department for Companion Animals and Horses, University of Veterinary Medicine Vienna, Vienna, Austria
| | - Luke C. Dutton
- Department of Clinical Sciences and Services, Royal Veterinary College, Hertfordshire, United Kingdom
| | - David J. Connolly
- Clinical Unit of Small Animal Surgery, Department for Companion Animals and Horses, University of Veterinary Medicine Vienna, Vienna, Austria
| | - Frank G. van Steenbeek
- Department of Clinical Sciences of Companion Animals, Faculty of Veterinary Medicine, Utrecht University, Utrecht, Netherlands
| | - Jayesh Dudhia
- Department of Clinical Sciences and Services, Royal Veterinary College, Hertfordshire, United Kingdom
| | - Louis C. Penning
- Department of Clinical Sciences of Companion Animals, Faculty of Veterinary Medicine, Utrecht University, Utrecht, Netherlands
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Wu X, Jiang J, Gu Z, Zhang J, Chen Y, Liu X. Mesenchymal stromal cell therapies: immunomodulatory properties and clinical progress. Stem Cell Res Ther 2020; 11:345. [PMID: 32771052 PMCID: PMC7414268 DOI: 10.1186/s13287-020-01855-9] [Citation(s) in RCA: 189] [Impact Index Per Article: 37.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2020] [Revised: 07/09/2020] [Accepted: 07/27/2020] [Indexed: 02/08/2023] Open
Abstract
Mesenchymal stromal cells (MSCs) are a subset of heterogeneous non-hematopoietic fibroblast-like cells that can differentiate into cells of multiple lineages, such as chondrocytes, osteoblasts, adipocytes, myoblasts, and others. These multipotent MSCs can be found in nearly all tissues but mostly located in perivascular niches, playing a significant role in tissue repair and regeneration. Additionally, MSCs interact with immune cells both in innate and adaptive immune systems, modulating immune responses and enabling immunosuppression and tolerance induction. Understanding the biology of MSCs and their roles in clinical treatment is crucial for developing MSC-based cellular therapy for a variety of pathological conditions. Here, we review the progress in the study on the mechanisms underlying the immunomodulatory and regenerative effects of MSCs; update the medical translation of MSCs, focusing on the registration trials leading to regulatory approvals; and discuss how to improve therapeutic efficacy and safety of MSC applications for future.
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Affiliation(s)
- Xiaomo Wu
- Dermatology Institute of Fuzhou, Dermatology Hospital of Fuzhou, Xihong Road 243, Fuzhou, 350025, China
- Department of Biomedicine, University of Basel, Klingelbergstr 70, CH-4056, Basel, Switzerland
| | - Ju Jiang
- Dermatology Institute of Fuzhou, Dermatology Hospital of Fuzhou, Xihong Road 243, Fuzhou, 350025, China
| | - Zhongkai Gu
- The Institute of Biomedical Sciences, Fudan University, Mingdao Building, Dongan Road 131, Shanghai, 200032, China
| | - Jinyan Zhang
- Dermatology Institute of Fuzhou, Dermatology Hospital of Fuzhou, Xihong Road 243, Fuzhou, 350025, China
| | - Yang Chen
- Dermatology Institute of Fuzhou, Dermatology Hospital of Fuzhou, Xihong Road 243, Fuzhou, 350025, China.
| | - Xiaolong Liu
- The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Xihong Road 312, Fuzhou, 350025, China.
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Abstract
PURPOSE OF REVIEW Osteogenesis imperfecta (OI) is a chronic disease with few treatment options available. The purpose of this review is to provide an overview on treating OI with mesenchymal stem cells (MSC). RECENT FINDINGS Off-the-shelf MSC have a good safety profile and exhibit multilineage differentiation potential and a low immunogenic profile and are easy to manufacture. Their ability to migrate, engraft, and differentiate into bone cells, and also to act via paracrine effects on the recipient's tissues, makes MSC candidates as a clinical therapy for OI. Due to their high osteogenic potency, fetal MSC offer an even higher therapeutic potential in OI compared with MSC derived from adult sources. Preclinical and initial clinical data support the use of MSC in treating OI. The characteristics of MSC make them of great interest in treating OI. MSC may be safely transplanted via intravenous administration and show potential positive clinical effects.
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Affiliation(s)
- Cecilia Götherström
- Department of Clinical Science, Intervention and Technology, Division of Obstetrics and Gynecology, Karolinska Institutet, ANA Futura, floor 8, Alfred Nobels Allé 8, 141 52 Huddinge, Stockholm, Sweden.
| | - Lilian Walther-Jallow
- Department of Clinical Science, Intervention and Technology, Division of Obstetrics and Gynecology, Karolinska Institutet, ANA Futura, floor 8, Alfred Nobels Allé 8, 141 52 Huddinge, Stockholm, Sweden
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Bao Z, Li J, Zhang P, Pan Q, Liu B, Zhu J, Jian Q, Jia D, Yi C, Moeller CJ, Liu H. Toll-Like Receptor 3 Activator Preconditioning Enhances Modulatory Function of Adipose‑Derived Mesenchymal Stem Cells in a Fully MHC-Mismatched Murine Model of Heterotopic Heart Transplantation. Ann Transplant 2020; 25:e921287. [PMID: 32366814 PMCID: PMC7219555 DOI: 10.12659/aot.921287] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
Background Donor-specific tolerance is the ultimate goal in organ transplantation. Diverse approaches, including the use of mesenchymal stem cells (MSCs), have been investigated to induce graft tolerance. Non-stimulated MSCs showed limited regulatory functions through interaction with multiple immune-regulatory cells, such as regulatory T cells (Tregs). To augment their functions, MSCs have been preconditioned with toll-like receptor (TLR3/4) agonist in autoimmune disease models, but results were conflicting. Material/Methods We evaluated the immunomodulatory effects of mouse adipose-derived mesenchymal stem cells (ADSCs) preconditioned with various combinations of TLR3/4 agonist and antagonists, including polyinosinic-polycytidylic acid poly(I:C)-TLR3 agonist, lipopolysaccharide (LPS) -TLR4 agonist, and TAK242-TLR4 antagonist. In vitro and in vivo experiments including mixed lymphocyte reaction, cytokines measurement, Tregs analysis, and a fully mismatched MHC heterotopic heart transplantation in mice (BALB/c to C57BL/6) were conducted. Results ADSCs preconditioned with poly(I:C) showed the highest efficiency in inhibiting lymphocyte proliferation, which was correlated with the upregulation of fibrinogen-like protein 2 (FGL2), an effector molecule of Tregs. The mean survival of cardiac allografts was extended from 8 to 12 days by intravenous injection of a single dose of ADSCs preconditioned with TLR3 agonist. The proportion of Tregs in the recipient’s spleen was significantly increased by injecting the poly(I:C)-stimulated ADSCs. Conclusions These results show that short-term TLR3 agonist preconditioning enhances the immunomodulatory efficacy of ADSCs, which can induce the generation of Tregs and upregulate the expression of FGL2, thereby improving the outcome of patients receiving organ transplantation.
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Affiliation(s)
- Zhiye Bao
- Department of Organ Transplantation and Hepatobiliary Surgery, The First Hospital of China Medical University, Shenyang, Liaoning, China (mainland).,The Key Laboratory of Organ Transplantation in Liaoning Province, Shenyang, Liaoning, China (mainland)
| | - Jingjing Li
- Department of Pediatric Surgery, Tianjin Children's Hospital, Tianjin, China (mainland)
| | - Pengju Zhang
- Oncology Center of People's Liberation Army (PLA), 81st Hospital Affiliated to Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China (mainland)
| | - Qi Pan
- Department of Organ Transplantation and Hepatobiliary Surgery, The First Hospital of China Medical University, Shenyang, Liaoning, China (mainland).,The Key Laboratory of Organ Transplantation in Liaoning Province, Shenyang, Liaoning, China (mainland)
| | - Boqian Liu
- Department of Organ Transplantation and Hepatobiliary Surgery, The First Hospital of China Medical University, Shenyang, Liaoning, China (mainland).,The Key Laboratory of Organ Transplantation in Liaoning Province, Shenyang, Liaoning, China (mainland)
| | - Jiayi Zhu
- Department of Organ Transplantation and Hepatobiliary Surgery, The First Hospital of China Medical University, Shenyang, Liaoning, China (mainland).,The Key Laboratory of Organ Transplantation in Liaoning Province, Shenyang, Liaoning, China (mainland)
| | - Qian Jian
- Department of Organ Transplantation and Hepatobiliary Surgery, The First Hospital of China Medical University, Shenyang, Liaoning, China (mainland).,The Key Laboratory of Organ Transplantation in Liaoning Province, Shenyang, Liaoning, China (mainland)
| | - Degong Jia
- Department of Organ Transplantation and Hepatobiliary Surgery, The First Hospital of China Medical University, Shenyang, Liaoning, China (mainland).,The Key Laboratory of Organ Transplantation in Liaoning Province, Shenyang, Liaoning, China (mainland)
| | - Caiyu Yi
- China Medical University, Shenyang, Liaoning, China (mainland)
| | | | - Hao Liu
- The Key Laboratory of Organ Transplantation in Liaoning Province, Shenyang, Liaoning, China (mainland)
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Li JN, Li W, Cao LQ, Liu N, Zhang K. Efficacy of mesenchymal stem cells in the treatment of gastrointestinal malignancies. World J Gastrointest Oncol 2020; 12:365-382. [PMID: 32368316 PMCID: PMC7191336 DOI: 10.4251/wjgo.v12.i4.365] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/02/2020] [Revised: 03/03/2020] [Accepted: 03/26/2020] [Indexed: 02/06/2023] Open
Abstract
Mesenchymal stem cells (MSCs), which are a kind of stem cell, possess an immune privileged nature, tumour homing features, and multi-lineage differentiation ability. MSCs have been studied in many fields, such as tissue engineering, nervous system diseases, and cancer treatment. In recent years, an increasing number of researchers have focused on the effects of MSCs on various kinds of tumours. However, the concrete anticancer efficacy of MSCs is still controversial. Gastrointestinal (GI) malignancies are the major causes of cancer-related death worldwide. The interactions of MSCs and GI cancer cells in specific conditions have attracted increasing attention. In this review, we introduce the characteristics of MSCs and analyse the effects of MSCs on GI malignancies, including gastric cancer, hepatoma, pancreatic cancer, and colorectal cancer. In addition, we also provide our perspectives on why MSCs may play different roles in GI malignancies and further research directions to increase the treatment efficacy of MSCs on GI malignancies.
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Affiliation(s)
- Jian-Nan Li
- Department of General Surgery, The Second Hospital of Jilin University, Changchun 130041, Jilin Province, China
| | - Wei Li
- Department of General Surgery, The Second Hospital of Jilin University, Changchun 130041, Jilin Province, China
| | - Lan-Qing Cao
- Department of Pathology, The Second Hospital of Jilin University, Changchun 130041, Jilin Province, China
| | - Ning Liu
- Department of Central Laboratory, The Second Hospital of Jilin University, Changchun 130041, Jilin Province, China
| | - Kai Zhang
- Department of General Surgery, The Second Hospital of Jilin University, Changchun 130041, Jilin Province, China
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Margaryan R, Assanta N, Menciassi A, Burchielli S, Matteucci M, Agostini S, Lionetti V, Luchi C, Cariati E, Pucci A, Coceani F, Murzi B. Selective perfusion of coronary vasculature in preterm sheep: a methodological innovation undermined by unfavourable operation of the foramen ovale. Can J Physiol Pharmacol 2020; 98:211-218. [PMID: 32202442 DOI: 10.1139/cjpp-2018-0648] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/30/2023]
Abstract
Antenatal cardiac intervention affords new prospects for hypoplastic left heart syndrome. Its success, however, may come not only from absence of impediments to blood flow but also from a sufficiently developed cardiac wall. Here, we examined the feasibility to perfuse selectively the fetal coronary circulation for treatment with growth promoting agents. Pregnant sheep (94-114 days gestation, term 145 days) were used. An aortic stop-flow procedure was developed for intracoronary access in the nonexposed fetus and human mesenchymal stem cells and their exosomes served as test agents. We found that aortic stop-flow ensures preferential distribution of fluorescent microspheres to the heart. However, intracoronary administration of stem cells or exosomes was detrimental, with fetal demise occurring around surgery or at variable intervals afterwards. Coincidentally, stop-flow caused by itself a marked rise of intraluminal pressure within the occluded aorta along with histological signs of coronary obstruction. We conclude that it is feasible to perfuse selectively the coronary circulation of the preterm fetus, but treatments are not compatible with survival of the animals. The cause for failure is found in the absence of hemodynamic compensation to stop-flow via a left-to-right shunt. This unexpected event is attributed to a largely membranous foramen ovale, characteristic of sheep, that collapses under pressure.
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Affiliation(s)
- Rafik Margaryan
- Fondazione Toscana Gabriele Monasterio, 54100 Massa and 56100 Pisa, Italy
| | - Nadia Assanta
- Fondazione Toscana Gabriele Monasterio, 54100 Massa and 56100 Pisa, Italy
| | - Arianna Menciassi
- Institute of BioRobotics, Scuola Superiore Sant'Anna, 56100 Pisa, Italy
| | - Silvia Burchielli
- Fondazione Toscana Gabriele Monasterio, 54100 Massa and 56100 Pisa, Italy
| | - Marco Matteucci
- Institute of Life Sciences, Scuola Superiore Sant'Anna, 56100 Pisa, Italy
| | - Silvia Agostini
- Institute of Life Sciences, Scuola Superiore Sant'Anna, 56100 Pisa, Italy
| | - Vincenzo Lionetti
- Institute of Life Sciences, Scuola Superiore Sant'Anna, 56100 Pisa, Italy
| | - Carlo Luchi
- Division of Prenatal Medicine, Pisa University Hospital, 56100 Pisa, Italy
| | - Ettore Cariati
- Department for Infant and Mother Care, Tuscany Center University Hospital, 50100 Florence, Italy
| | - Angela Pucci
- Department of Pathology, Pisa University Hospital, 56100 Pisa, Italy
| | - Flavio Coceani
- Institute of Life Sciences, Scuola Superiore Sant'Anna, 56100 Pisa, Italy
| | - Bruno Murzi
- Fondazione Toscana Gabriele Monasterio, 54100 Massa and 56100 Pisa, Italy
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Kawashima A, Yasuhara R, Akino R, Mishima K, Nasu M, Sekizawa A. Engraftment potential of maternal adipose-derived stem cells for fetal transplantation. Heliyon 2020; 6:e03409. [PMID: 32154403 PMCID: PMC7057202 DOI: 10.1016/j.heliyon.2020.e03409] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/04/2018] [Revised: 02/05/2020] [Accepted: 02/07/2020] [Indexed: 01/05/2023] Open
Abstract
Advances in prenatal molecular testing have made it possible to diagnose most genetic disorders early in gestation. In utero mesenchymal stem cell (MSC) therapy can be a powerful tool to cure the incurable. With this in mind, this method could ameliorate potential physical and functional damage. However, the presence of maternal T cells trafficking in the fetus during pregnancy is thought to be the major barrier to achieving the engraftment into the fetus. We investigated the possibility of using maternal adipose-derived stem cells (ADSCs) for in utero transplantation to improve engraftment, thus lowering the risk of graft rejection. Herein, fetal brain engraftment using congenic and maternal ADSC grafts was examined via in utero stem cell transplantation in a mouse model. ADSCs were purified using the mesenchymal stem cell markers, PDGFRα, and Sca-1 via fluorescence-activated cell sorting. The PDGFRα+Sca-1+ ADSCs were transplanted into the fetal intracerebroventricular (ICV) at E14.5. The transplanted grafts grew for at least 28 days after in utero transplantation with PDGFRα+Sca-1+ ADSC, and mature neuronal markers were also detected in the grafts. Furthermore, using the maternal sorted ADSCs suppressed the innate immune response, preventing the infiltration of CD8 T cells into the graft. Thus, in utero transplantation into the fetal ICV with the maternal PDGFRα+Sca-1+ ADSCs may be beneficial for the treatment of congenital neurological diseases because of the ability to reduce the responses after in utero stem cell transplantation and differentiate into neuronal lineages.
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Affiliation(s)
- Akihiro Kawashima
- Department of Obstetrics and Gynecology, Showa University School of Medicine, 1-5-8 Hatanodai, Shinagawa, Tokyo, 142-8666, Japan
| | - Rika Yasuhara
- Division of Pathology, Department of Oral Diagnostic Sciences, Showa University School of Dentistry, 1-5-8 Hatanodai, Shinagawa, Tokyo, 142-8555, Japan
| | - Ryosuke Akino
- Department of Obstetrics and Gynecology, Showa University School of Medicine, 1-5-8 Hatanodai, Shinagawa, Tokyo, 142-8666, Japan
| | - Kenji Mishima
- Division of Pathology, Department of Oral Diagnostic Sciences, Showa University School of Dentistry, 1-5-8 Hatanodai, Shinagawa, Tokyo, 142-8555, Japan
| | - Michiko Nasu
- Department of Obstetrics and Gynecology, Showa University School of Medicine, 1-5-8 Hatanodai, Shinagawa, Tokyo, 142-8666, Japan
| | - Akihiko Sekizawa
- Department of Obstetrics and Gynecology, Showa University School of Medicine, 1-5-8 Hatanodai, Shinagawa, Tokyo, 142-8666, Japan
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Liu H, Chen W, Zhao B, Quan W, Zhang Y, Zhou Y, Wan Z, Zhang X, Xue G, Li J, Luo S, Wang J, Liu Y, Zhen M, Zhao Y. Autologous bionic tissue for inguinal hernia repair. J Biomed Mater Res A 2020; 108:1351-1368. [PMID: 32090432 DOI: 10.1002/jbm.a.36907] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2019] [Revised: 02/14/2020] [Accepted: 02/17/2020] [Indexed: 11/07/2022]
Abstract
The prosthetic mesh, which is widely used in tension-free hernioplasty, often result in avascular stiff fibrotic scar or mesh shrinkage, causing chronic pain and infection. Here, we developed an autologous bionic tissue (ABT), which was composed of autologous bone marrow-derived mesenchymal stem cells (MSCs), poly (lactic-co-glycolic acid) (PLGA) porous scaffolds, and extracellular matrix (ECM) produced by MSCs for inguinal hernioplasty. In ABT, MSCs produced a variety of ECM composites, such as structural proteins (insoluble collagen, elastin) that provided mechanical properties, macromolecules (hyaluronic acid, glycosaminoglycan) as water and cytokines reservoir, and cell-engaging proteins (fibronectin, laminin). The above ECM composites reached the highest level in 21 days. ECM degradation related cytokines (MMP-9 and its inhibitor TIMP-1) reached the highest level on the 14th day. ECM increased the mechanical properties, elasticity, and flexibility of PLGA. Compared with the PLGA, ABT greatly inhibited inflammatory factors and promoted anti-inflammatory factors (p < 0.05), and gradually reduced the M1/M2 ratio in vivo (p < 0.05). After implantation, the thickness of tissue regeneration (p < 0.05), the number of capillaries or mature vessels (p < 0.05), the mechanical properties of ABT (p < 0.05) were greater than PLGA. MSCs and ECM could reduce the inflammation caused by PLGA, and prevent PLGA from earlier degradation and facilitate host cellular infiltration, thus ABT could greatly promote tissue regeneration in hernia repairs.
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Affiliation(s)
- Hongyi Liu
- School of Medicine, Xiamen University, Xiamen, Fujian Province, People's Republic of China
| | - Weibin Chen
- School of Medicine, Xiamen University, Xiamen, Fujian Province, People's Republic of China
| | - Bin Zhao
- School of Medicine, Xiamen University, Xiamen, Fujian Province, People's Republic of China
| | - Wei Quan
- School of Medicine, Xiamen University, Xiamen, Fujian Province, People's Republic of China
| | - Yinlong Zhang
- School of Medicine, Xiamen University, Xiamen, Fujian Province, People's Republic of China
| | - Yuanyuan Zhou
- School of Medicine, Xiamen University, Xiamen, Fujian Province, People's Republic of China
| | - Zheng Wan
- School of Medicine, Xiamen University, Xiamen, Fujian Province, People's Republic of China
| | - Xiaohong Zhang
- School of Medicine, Xiamen University, Xiamen, Fujian Province, People's Republic of China
| | - Gang Xue
- School of Medicine, Xiamen University, Xiamen, Fujian Province, People's Republic of China
| | - Jietao Li
- School of Medicine, Xiamen University, Xiamen, Fujian Province, People's Republic of China
| | - Shuting Luo
- School of Medicine, Xiamen University, Xiamen, Fujian Province, People's Republic of China
| | - Jinling Wang
- Emergency, Zhongshan Hospital, Xiamen University, Xiamen, Fujian Province, People's Republic of China
| | - Yun Liu
- Hepatology Surgery, Zhongshan Hospital, Xiamen University, Xiamen, Fujian Province, People's Republic of China
| | - Maochuan Zhen
- Hepatology Surgery, Zhongshan Hospital, Xiamen University, Xiamen, Fujian Province, People's Republic of China
| | - Yilin Zhao
- Oncology and Vascular Interventional Radiology, Zhongshan Hospital, Xiamen University, Xiamen, Fujian Province, People's Republic of China
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Conditioned Medium from Adipose-Derived Stem Cell Inhibits Jurkat Cell Proliferation through TGF- β1 and p38/MAPK Pathway. Anal Cell Pathol (Amst) 2020; 2019:2107414. [PMID: 31934530 PMCID: PMC6942699 DOI: 10.1155/2019/2107414] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/06/2019] [Revised: 08/10/2019] [Accepted: 08/26/2019] [Indexed: 02/05/2023] Open
Abstract
Background Since the first report on the immunomodulatory and immunosuppressive properties of Adipose-Derived Stem Cells (ADSCs), many studies have elucidated the underlying molecular mechanism of their suppressive activity on mixed lymphocyte reaction (MLR). However, a gap exists in our understanding of the molecular mechanism of ADSC-conditioned medium (ADSC-CM) on MLR. Methods ADSCs were isolated from Human Adipose Tissues, and Enzyme-linked Immunosorbent Assay (ELISA) was used to identify the concentration of transforming growth factor β1 (TGF-β1) in ADSC-CM. The transcript abundance of TGF-β1, as well as that of insulin-like growth factor binding protein 3 (IGF-BP3), was evaluated using qRT-PCR on Jurkat cells cultured in ADSC-CM for 24 hours. The proliferation of the Jurkat cells was assessed using cell cycle assay. Western blotting was performed to identify potential signaling molecules involved in the ADSC-CM-induced inhibition of Jurkat cell proliferation. Results The findings confirm that the isolated ADSCs demonstrate classic ADSC characteristics. The level of TGF-β1 was found to be low in ADSC-CM, as assessed by ELISA. Jurkat cells grown in ADSC-CM show reduced gene expression of TGF-β1 and IGF-BP3 compared with that of the control group. Furthermore, western blotting of ADSC-CM grown Jurkat cells that were blocked at the G0/G1 stage indicates that ADSC-CM decreases the protein expression of pP38 in a dose-dependent manner. Conclusion ADSC-CM can inhibit Jurkat cell proliferation through the TGF-β1-p38 signaling pathway.
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Lu Y, Zhou Y, Ju R, Chen J. Human-animal chimeras for autologous organ transplantation: technological advances and future perspectives. ANNALS OF TRANSLATIONAL MEDICINE 2019; 7:576. [PMID: 31807557 DOI: 10.21037/atm.2019.10.13] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
Organ transplantation is the most promising curation for end-stage organ disease. However, the donor organ shortage has become a global problem that has limited the development of organ transplantation. Human-animal chimeras provide the ability to produce human organs in other species using autologous stem cells [e.g., induced pluripotent stem cells (iPSCs) or adult stem cells], which would be patient-specific and immune-matched for transplantation. Due to the potential application prospect of interspecies chimeras in basic and translational research, this technology has attracted much interest. This review focuses primarily on technological advances, including options of donor stem cell types and gene editing in donor cells and host animals, in addition to perspectives on human-animal chimeras in clinical and basic research.
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Affiliation(s)
- Yingfei Lu
- Central Laboratory, Translational Medicine Research Center, The Affiliated Jiangning Hospital with Nanjing Medical University, Nanjing 211100, China
| | - Yu Zhou
- Central Laboratory, Translational Medicine Research Center, The Affiliated Jiangning Hospital with Nanjing Medical University, Nanjing 211100, China.,Department of Obstetrics and Gynecology, The Affiliated Jiangning Hospital with Nanjing Medical University, Nanjing 211100, China
| | - Rong Ju
- Department of Obstetrics and Gynecology, The Affiliated Jiangning Hospital with Nanjing Medical University, Nanjing 211100, China
| | - Jianquan Chen
- Central Laboratory, Translational Medicine Research Center, The Affiliated Jiangning Hospital with Nanjing Medical University, Nanjing 211100, China.,Department of Obstetrics and Gynecology, The Affiliated Jiangning Hospital with Nanjing Medical University, Nanjing 211100, China
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50
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Sim SW, Weinstein DA, Lee YM, Jun HS. Glycogen storage disease type Ib: role of glucose‐6‐phosphate transporter in cell metabolism and function. FEBS Lett 2019; 594:3-18. [PMID: 31705665 DOI: 10.1002/1873-3468.13666] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2019] [Revised: 10/16/2019] [Accepted: 10/25/2019] [Indexed: 12/19/2022]
Affiliation(s)
- Sang Wan Sim
- Department of Biotechnology and Bioinformatics College of Science and Technology Korea University Sejong Korea
| | - David A. Weinstein
- Glycogen Storage Disease Program University of Connecticut School of Medicine Farmington CT USA
| | - Young Mok Lee
- Glycogen Storage Disease Program University of Connecticut School of Medicine Farmington CT USA
| | - Hyun Sik Jun
- Department of Biotechnology and Bioinformatics College of Science and Technology Korea University Sejong Korea
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