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Nie P, Qin W, Nie WC, Li B. Progress in the application of mesenchymal stem cells to attenuate apoptosis in diabetic kidney disease. World J Diabetes 2025; 16:105711. [DOI: 10.4239/wjd.v16.i6.105711] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/16/2025] [Revised: 03/24/2025] [Accepted: 04/25/2025] [Indexed: 06/13/2025] Open
Abstract
Diabetic kidney disease (DKD) has a high incidence and mortality rate and lacks effective preventive and therapeutic methods. Apoptosis is one of the main reasons for the occurrence and development of DKD. Mesenchymal stem cells (MSCs) have shown great promise in tissue regeneration for DKD treatment and have protective effects against DKD, including decreased blood glucose and urinary protein levels and improved renal function. MSCs can directly differentiate into kidney cells or act via paracrine mechanisms to reduce apoptosis in DKD by modulating signaling pathways. MSC-derived extracellular vesicles (MSC-EVs) mitigate apoptosis and DKD-related symptoms by transferring miRNAs to target cells or organs. However, studies on the regulatory mechanisms of MSCs and MSC-EVs in apoptosis in DKD are insufficient. This review comprehensively examines the mechanisms of apoptosis in DKD and research progress regarding the roles of MSCs and MSC-EVs in the disease process.
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Affiliation(s)
- Ping Nie
- Department of Nephropathy, The Second Hospital of Jilin University, Changchun 130041, Jilin Province, China
| | - Wei Qin
- Department of Nephropathy, The Second Hospital of Jilin University, Changchun 130041, Jilin Province, China
| | - Wei-Chen Nie
- Basic Clinical Specialization in Integrative Chinese and Western Medicine, Changchun University of Chinese Medicine, Changchun 130117, Jilin Province, China
| | - Bing Li
- Department of Nephropathy, The Second Hospital of Jilin University, Changchun 130041, Jilin Province, China
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Xiang YY, Won JH, Kim JS, Baek KW. Transplantation of Exercise-Enhanced Mesenchymal Stem Cells Improves Obesity and Glucose Tolerance via Immune Modulation in Adipose Tissue. Stem Cell Rev Rep 2025:10.1007/s12015-025-10881-0. [PMID: 40227488 DOI: 10.1007/s12015-025-10881-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 04/07/2025] [Indexed: 04/15/2025]
Abstract
Exercise-conditioned mesenchymal stem cells (MSCs) may modulate immune responses and improve white adipose tissue (WAT) function. While MSCs are known to reduce inflammation, it remains unclear if exercise-stimulated MSCs can improve obesity-related dysfunctions. This study is the first to explore how exercise-conditioned MSCs may influence adipose tissue inflammation and remodeling in the context of obesity. MSCs were isolated from exercised- and sedentary donor mice, then cultured in vitro. After culture, MSCs were assessed for differentiation capacity and cytokine gene expression, including Il10, as indicators of immune modulation. Exercise-conditioned MSCs were then transplanted into obese recipient mice. Following transplantation, immune cell profiles, inflammatory markers, and adipocyte morphology in recipient WAT were analyzed. Flow cytometry was used to quantify macrophage subtypes (pro-inflammatory and anti-inflammatory), and histological analysis was performed to measure changes in adipocyte size. Exercise-activated MSCs showed a ± 35% increase in Il10 expression and a ± 20% enhancement in differentiation capacity compared to controls, indicating improved immunomodulatory potential. In recipient mice, transplantation led to a ± 25% reduction in pro-inflammatory macrophages (CD86+ CD206-) and a 15% decrease in adipocyte size within WAT. Additionally, WAT in treated mice showed balanced inflammatory profiles and reduced adipose hypertrophy, suggesting restored immune balance and metabolic health. These findings suggest that exercise-modified MSCs exhibit enhanced immunomodulatory and metabolic regulatory properties. This study provides evidence that exercise enhances MSC characteristics, potentially improving their capacity to modulate adipose tissue immune balance and metabolic function in obesity. Exercise-conditioned MSCs may serve as a foundation for future strategies that integrate exercise-induced stem cell modifications to modulate obesity-related metabolic dysfunction.
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Affiliation(s)
- Ying-Ying Xiang
- Department of Physical Education, Gyeongsang National University, Jinju, 52828, Korea
| | - Jong-Hwa Won
- Department of Physical Education, Gyeongsang National University, Jinju, 52828, Korea
| | - Ji-Seok Kim
- Department of Physical Education, Gyeongsang National University, Jinju, 52828, Korea
- Research Institute of Pharmaceutical Sciences, Gyeongsang National University, Jinju, 52828, Korea
| | - Kyung-Wan Baek
- Department of Physical Education, Gyeongsang National University, Jinju, 52828, Korea.
- Research Institute of Pharmaceutical Sciences, Gyeongsang National University, Jinju, 52828, Korea.
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Meligy FY, Mohammed HSED, Abou Elghait AT, Mohamed HK, Ashry IESM, Abdel-Rahman Sayed A, Hussein OA, Salman A, Atia T, Mohamed AS, Behnsawy NH, Gaber SS, Sakr HI, Ahmed SF. Mesenchymal stem cells versus mesenchymal stem cells-derived exosomes as potential autophagy pathway modulators in a diabetic model. Adv Med Sci 2025; 70:152-165. [PMID: 39956208 DOI: 10.1016/j.advms.2025.02.004] [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: 08/06/2024] [Revised: 12/06/2024] [Accepted: 02/13/2025] [Indexed: 02/18/2025]
Abstract
PURPOSE This work compared the potential effects of bone marrow mesenchymal stem cells (BM-MSCs) with BM-MSCs-derived exosomes against impaired autophagy in streptozotocin (STZ)-induced diabetic rats. MATERIALS AND METHODS Three days after STZ injection, a single dose of (3 × 10^6) BM- MSCs or BM-MSCs-derived exosomes (80 μg/rat) was administered to evaluate their effects against nondiabetic and diabetic control rats. We assessed pancreatic structure via light and electron microscopy and evaluated its staining for insulin and the autophagy marker P62 immunohistochemically. Moreover, autophagy marker LC3 gene expression was examined by PCR. RESULTS Both BM-MSCs and BM-MSCs derived exosomes showed histological restoration of pancreatic tissues. Both treatments markedly increased the amount of insulin and significantly decreased the autophagy markers P62 and LC3. CONCLUSION Our findings suggest that both BM-MSCs and BM-MSCs-derived exosomes provides a potential alternative to modulate diabetes mellitus.
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Affiliation(s)
- Fatma Y Meligy
- Department of Restorative Dentistry and Basic Medical Sciences, Faculty of Dentistry, University of Petra, Amman, Jordan; Histology and Cell Biology Department, Faculty of Medicine, Assiut University, Assiut, Egypt
| | | | - Amal T Abou Elghait
- Histology and Cell Biology Department, Faculty of Medicine, Assiut University, Assiut, Egypt; Histology and Cell Biology Department, Sphinx University, New Assiut city, Assiut, Egypt
| | - Heba K Mohamed
- Anatomy and Embryology Department, Faculty of Medicine, Assiut University, Assiut, Egypt; Anatomy and Embryology Department, Sphinx University, New Assiut city, Assiut, Egypt
| | | | - Ayat Abdel-Rahman Sayed
- Medical Biochemistry Department, Faculty of Medicine, Assiut University, Assiut, Egypt; Department of Biochemistry, Sphinx University, New Assiut city, Assiut, Egypt
| | - Ola A Hussein
- Histology and Cell Biology Department, Faculty of Medicine, Assiut University, Assiut, Egypt
| | - Ahmed Salman
- Department of Anatomy and Histology, Faculty of Medicine, The University of Jordan, Amman, Jordan; Department of Anatomy, Faculty of Medicine, Menoufia University, Menoufia, Egypt
| | - Tarek Atia
- Department of Medical Laboratories, College of Applied Medical Sciences, Prince Sattam Bin Abdulaziz University, Al-Kharj, Saudi Arabia
| | - Abir S Mohamed
- Department of Public Health, College of Nursing and Health Sciences, Jazan University, Jazan, Saudi Arabia
| | - Nour H Behnsawy
- Faculty of Medicine, Assiut University, Assiut, Egypt; Skilled Medical Practitioners Focus Area Coordinator 24/25, International Federation of Medical Students Association, Egypt
| | - Safy Salah Gaber
- Department of Medical Physiology, Faculty of Medicine, Beni-Suef University, Beni-Suef, Egypt
| | - Hader I Sakr
- Department of Medical Physiology, Faculty of Medicine, Cairo University, Cairo, Egypt; Department of Medical Physiology, General Medicine Practice Program, Batterjee Medical College, Jeddah, 21442, Saudi Arabia.
| | - Salwa Fares Ahmed
- Histology and Cell Biology Department, Faculty of Medicine, Assiut University, Assiut, Egypt; Anatomy Department, Faculty of Medicine, University of Tabuk, Tabuk, Saudi Arabia
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Ghassemifard L, Hasanlu M, Parsamanesh N, Atkin SL, Almahmeed W, Sahebkar A. Cell Therapies and Gene Therapy for Diabetes: Current Progress. Curr Diabetes Rev 2025; 21:e130524229899. [PMID: 38747221 DOI: 10.2174/0115733998292392240425122326] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/11/2023] [Revised: 03/07/2024] [Accepted: 03/21/2024] [Indexed: 04/23/2025]
Abstract
The epidemic of diabetes continues to be an increasing problem, and there is a need for new therapeutic strategies. There are several promising drugs and molecules in synthetic medicinal chemistry that are developing for diabetes. In addition to this approach, extensive studies with gene and cell therapies are being conducted. Gene therapy is an existing approach in treating several diseases, such as cancer, autoimmune diseases, heart disease and diabetes. Several reports have also suggested that stem cells have the differentiation capability to functional pancreatic beta cell development in vitro and in vivo, with the utility to treat diabetes and prevent the progression of diabetes-related complications. In this current review, we have focused on the different types of cell therapies and vector-based gene therapy in treating or preventing diabetes.
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Affiliation(s)
- Leila Ghassemifard
- Department of Physiology, School of Medicine, Zanjan University of Medical Sciences, Zanjan, Iran
- Department of Persian Medicine, School of Medicine, Zanjan University of Medical Sciences, Zanjan, Iran
| | - Masumeh Hasanlu
- Department of Internal Medicine, Vali-e-Asr Hospital, School of Medicine, Zanjan University of Medical Sciences, Zanjan, Iran
| | - Negin Parsamanesh
- Metabolic Diseases Research Center, Zanjan University of Medical Sciences, Zanjan, Iran
- Department of Genetics and Molecular Medicine, School of Medicine, Zanjan University of Medical Sciences, Zanjan, Iran
| | - Stephen L Atkin
- Research Department, Royal College of Surgeons in Ireland Bahrain, Adliya, Bahrain
| | - Wael Almahmeed
- Heart and Vascular Institute, Cleveland Clinic Abu Dhabi, Abu Dhabi, United Arab Emirates
| | - Amirhossein Sahebkar
- Center for Global Health Research, Saveetha Medical College and Hospitals, Saveetha Institute of Medical and Technical Sciences, Saveetha University, Chennai, India
- Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran
- Applied Biomedical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
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Qin X, Liu J. Nanoformulations for the diagnosis and treatment of metabolic dysfunction-associated steatohepatitis. Acta Biomater 2024; 184:37-53. [PMID: 38879104 DOI: 10.1016/j.actbio.2024.06.014] [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: 12/30/2023] [Revised: 05/25/2024] [Accepted: 06/10/2024] [Indexed: 06/29/2024]
Abstract
Metabolic dysfunction-associated steatohepatitis (MASH) is a progressive phase of metabolic dysfunction-associated steatotic liver disease (MASLD) that develops into irreversible liver cirrhosis and hepatocellular carcinoma, ultimately necessitating liver transplantation as the sole life-saving option. However, given the drawbacks of liver transplantation, including invasiveness, chronic immunosuppression, and a lack of donor livers, prompt diagnosis and effective treatment are indispensable. Due to the limitations of liver biopsy and conventional imaging modalities in diagnosing MASH, as well as the potential hazards associated with liver-protecting medicines, numerous nanoformulations have been created for MASH theranostics. Particularly, there has been significant study interest in artificial nanoparticles, natural biomaterials, and bionic nanoparticles that exhibit exceptional biocompatibility and bioavailability. In this review, we summarized extracellular vesicles (EVs)-based omics analysis and Fe3O4-based functional magnetic nanoparticles as magnetic resonance imaging (MRI) contrast agents for MASH diagnosis. Additionally, artificial nanoparticles such as organic and inorganic nanoparticles, as well as natural biomaterials such as cells and cell-derived EVs and bionic nanoparticles including cell membrane-coated nanoparticles, have also been reported for MASH treatment owing to their specific targeting and superior therapeutic effect. This review has the potential to stimulate advancements in nanoformulation fabrication techniques. By exploring their compatibility with cell biology, it could lead to the creation of innovative material systems for efficient theragnostic uses for MASH. STATEMENT OF SIGNIFICANCE: People with metabolic dysfunction-associated steatohepatitis (MASH) will progress to fibrosis, cirrhosis, or even liver cancer. It is imperative to establish effective theragnostic techniques to stop MASH from progressing into a lethal condition. In our review, we summarize the advancement of artificial, natural, and bionic nanoparticles applied in MASH theragnosis. Furthermore, the issues that need to be resolved for these cutting-edge techniques are summarized to realize a more significant clinical impact. We forecast the key fields that will advance further as nanotechnology and MASH research progress. Generally, our discovery has significant implications for the advancement of nanoformulation fabrication techniques, and their potential to be compatible with cell biology could lead to the creation of innovative materials systems for effective MASH theragnostic.
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Affiliation(s)
- Xueying Qin
- Institute of Translational Medicine, Medical College, Yangzhou University, Yangzhou, 225001, PR China; The Key Laboratory of Syndrome Differentiation and Treatment of Gastric Cancer of the State Administration of Traditional Chinese Medicine, Yangzhou, 225001, PR China
| | - Jingjing Liu
- Institute of Translational Medicine, Medical College, Yangzhou University, Yangzhou, 225001, PR China; The Key Laboratory of Syndrome Differentiation and Treatment of Gastric Cancer of the State Administration of Traditional Chinese Medicine, Yangzhou, 225001, PR China.
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Yang Q, Chen Q, Li S, Luo J. Mesenchymal stem cells ameliorate inflammation and pyroptosis in diabetic cardiomyopathy via the miRNA-223-3p/NLRP3 pathway. Diabetol Metab Syndr 2024; 16:146. [PMID: 38956716 PMCID: PMC11221100 DOI: 10.1186/s13098-024-01389-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/21/2024] [Accepted: 06/25/2024] [Indexed: 07/04/2024] Open
Abstract
BACKGROUND Diabetic cardiomyopathy (DCM) stands as the primary cause of heart failure and mortality among patients with diabetes. Nevertheless, conventional treatment approaches are limited in their ability to effectively prevent myocardial tissue damage itself. Mesenchymal stem cell (MSC) therapy exhibits immense potential for treating DCM; however, the precise mechanisms involved in regulating inflammatory responses and pyroptosis processes, an emerging form of cellular death, within myocardial cells remain elusive. Hence, it is imperative to further elucidate the precise underlying mechanisms to facilitate the clinical implementation of MSC therapy. METHODS In vivo, we established a DCM mouse model by administering streptozotocin and fed the mice a high-glucose and high-fat diet, followed by MSC therapy. Cardiac function and myocardial injury were evaluated through echocardiography and histological analysis. Furthermore, the levels of inflammation and pyroptosis were assessed using ELISA, Western blotting, and qRT-PCR. In vitro experiments involved inducing H9C2 myocardial cell damage with high glucose treatment, followed by coculture with MSCs to investigate their role in modulating inflammation and pyroptosis mechanisms. RESULTS MSCs can maintain cardiac function and alleviate myocardial injury in mice with DCM. Moreover, they effectively suppress the activation of NLRP3 and reduce the release of inflammatory factors (such as IL-1β and ROS), thereby further downregulating the expression of pyroptosis-related proteins including NLRP3, Caspase-1, and GSDMD. Additionally, we experimentally validated that MSCs exert their therapeutic effects by promoting the expression of miR-223-3p in cardiac myocytes; however, this effect can be reversed by an miR-223-3p inhibitor. CONCLUSION MSCs effectively mitigate the release of inflammatory factors and cell lysis caused by pyroptosis through the regulation of the miR-223-3p/NLRP3 pathway, thereby safeguarding cardiomyocytes against damage in DCM. This mechanism establishes a novel theoretical foundation for the clinical treatment of cardiac conditions utilizing MSCs.
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Affiliation(s)
- Qu Yang
- Department of Rehabilitation Medicine, The 2nd Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, 330006, China
- Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, 330006, China
| | - Qi Chen
- Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, 330006, China
| | - Sihui Li
- Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, 330006, China
| | - Jun Luo
- Department of Rehabilitation Medicine, The 2nd Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, 330006, China.
- Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, 330006, China.
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He R, Chen Y. The Role of Adipose Tissue-derived Exosomes in Chronic Metabolic Disorders. Curr Med Sci 2024; 44:463-474. [PMID: 38900388 DOI: 10.1007/s11596-024-2902-2] [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: 11/08/2023] [Accepted: 05/28/2024] [Indexed: 06/21/2024]
Abstract
Excessive fat deposition in obese subjects promotes the occurrence of metabolic diseases, such as type 2 diabetes mellitus (T2DM), cardiovascular diseases, and non-alcoholic fatty liver disease (NAFLD). Adipose tissue is not only the main form of energy storage but also an endocrine organ that not only secretes adipocytokines but also releases many extracellular vesicles (EVs) that play a role in the regulation of whole-body metabolism. Exosomes are a subtype of EVs, and accumulating evidence indicates that adipose tissue exosomes (AT Exos) mediate crosstalk between adipose tissue and multiple organs by being transferred to targeted cells or tissues through paracrine or endocrine mechanisms. However, the roles of AT Exos in crosstalk with metabolic organs remain to be fully elucidated. In this review, we summarize the latest research progress on the role of AT Exos in the regulation of metabolic disorders. Moreover, we discuss the potential role of AT Exos as biomarkers in metabolic diseases and their clinical application.
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Affiliation(s)
- Rui He
- Division of Endocrinology, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China
- Laboratory of Endocrinology & Metabolism, Key Laboratory of Vascular Aging of the Ministry of Education, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China
| | - Yong Chen
- Division of Endocrinology, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
- Laboratory of Endocrinology & Metabolism, Key Laboratory of Vascular Aging of the Ministry of Education, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
- Branch of National Clinical Research Center for Metabolic Diseases, Wuhan, 430030, China.
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Shabani M, Sharifi S, Karimi I, Shirian S, Fadaei M, Mirzaei E. Evaluation of the restorative effect of ozone and chitosan-hyaluronic acid with and without mesenchymal stem cells on wound healing in rats. Vet Med Sci 2024; 10:e1439. [PMID: 38695208 PMCID: PMC11063917 DOI: 10.1002/vms3.1439] [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: 01/08/2024] [Accepted: 03/10/2024] [Indexed: 05/04/2024] Open
Abstract
This study evaluated the effect of ozone, chitosan-hyaluronic (Cs-HA) acid and mesenchymal stem cells (MSCs) on wound healing in rats. A total of 64 rats were randomly divided into four groups: control, ozone, Cs-HA + ozone and Cs-HA + ozone + MSCs. A 5 mm full-thickness wound was created on the back of each rat. The wound area was measured macroscopically on days 3, 5, 9 and 14. Tissue sections were prepared for histopathological evaluation of inflammation, collagen arrangement, neovascularization and epithelial tissue rearrangement. Macroscopic assessment showed differences in wound area on days 5, 9 and 14. Histopathological examination showed that the Cs-HA + ozone + MSCs and Cs-HA + ozone groups had significantly higher vascularization on day 3 compared to the ozone-treated and control groups. All treatment groups had significantly better collagen arrangement than the control group. On day 5, no significant difference was observed between different groups. On day 9, the inflammation level in the Cs-HA + ozone + MSCs group was significantly lower than in the other groups. All treatment groups had significantly better vascularization compared to the control group. On day 14, the rate of inflammation was significantly lower in the treatment groups than in the control group. Significantly higher collagen arrangement levels were observed in the Cs-HA + ozone and Cs-HA + ozone + MSCs groups compared to the control and ozone groups. All treatment groups had significantly better epithelial tissue rearrangement than the control group. Overall, the results of this study indicated that treatment with ozone, Cs-HA acid, Cs-HA and MSCs accelerated wound healing in rats. The effect of using Cs-HA acid with mesenchymal cells was better than the other types of treatment. Larger clinical trials are needed to assess these factors for improving chronic wound treatment.
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Affiliation(s)
- Mahshid Shabani
- Department of Clinical SciencesFaculty of Veterinary MedicineUniversity of ShahrekordShahrekordIran
- Shiraz Molecular Pathology Resrech CenterDr Daneshbod Path LabShirazIran
| | - Siavash Sharifi
- Department of Clinical SciencesFaculty of Veterinary MedicineUniversity of ShahrekordShahrekordIran
| | - Iraj Karimi
- Department of PathobiologySchool of Veterinary MedicineUniversity of ShahrekordShahrekordIran
| | - Sadegh Shirian
- Department of PathobiologySchool of Veterinary MedicineUniversity of ShahrekordShahrekordIran
| | - Milad Fadaei
- Department of Medical NanotechnologySchool of Advanced Medical Sciences and TechnologiesShiraz University of Medical SciencesShirazIran
| | - Esmaeil Mirzaei
- Department of Medical NanotechnologySchool of Advanced Medical Sciences and TechnologiesShiraz University of Medical SciencesShirazIran
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Yan D, Song Y, Zhang B, Cao G, Zhou H, Li H, Sun H, Deng M, Qiu Y, Yi W, Sun Y. Progress and application of adipose-derived stem cells in the treatment of diabetes and its complications. Stem Cell Res Ther 2024; 15:3. [PMID: 38167106 PMCID: PMC10763319 DOI: 10.1186/s13287-023-03620-0] [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: 08/01/2023] [Accepted: 12/19/2023] [Indexed: 01/05/2024] Open
Abstract
Diabetes mellitus (DM) is a serious chronic metabolic disease that can lead to many serious complications, such as cardiovascular disease, retinopathy, neuropathy, and kidney disease. Once diagnosed with diabetes, patients need to take oral hypoglycemic drugs or use insulin to control blood sugar and slow down the progression of the disease. This has a significant impact on the daily life of patients, requiring constant monitoring of the side effects of medication. It also imposes a heavy financial burden on individuals, their families, and even society as a whole. Adipose-derived stem cells (ADSCs) have recently become an emerging therapeutic modality for DM and its complications. ADSCs can improve insulin sensitivity and enhance insulin secretion through various pathways, thereby alleviating diabetes and its complications. Additionally, ADSCs can promote tissue regeneration, inhibit inflammatory reactions, and reduce tissue damage and cell apoptosis. The potential mechanisms of ADSC therapy for DM and its complications are numerous, and its extensive regenerative and differentiation ability, as well as its role in regulating the immune system and metabolic function, make it a powerful tool in the treatment of DM. Although this technology is still in the early stages, many studies have already proven its safety and effectiveness, providing new treatment options for patients with DM or its complications. Although based on current research, ADSCs have achieved some results in animal experiments and clinical trials for the treatment of DM, further clinical trials are still needed before they can be applied in a clinical setting.
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Affiliation(s)
- Dongxu Yan
- Department of General Medicine, Xijing Hospital, Fourth Military Medical University, 127# Changlexi Road, Xi'an, 710032, China
| | - Yujie Song
- Department of Cardiovascular Surgery, Xijing Hospital, Fourth Military Medical University, 127# Changlexi Road, Xi'an, 710032, China
| | - Bing Zhang
- Department of Cardiovascular Surgery, Xijing Hospital, Fourth Military Medical University, 127# Changlexi Road, Xi'an, 710032, China
| | - Guojie Cao
- Department of General Medicine, Xijing Hospital, Fourth Military Medical University, 127# Changlexi Road, Xi'an, 710032, China
| | - Haitao Zhou
- Department of General Medicine, Xijing Hospital, Fourth Military Medical University, 127# Changlexi Road, Xi'an, 710032, China
| | - Hong Li
- Department of General Medicine, Xijing Hospital, Fourth Military Medical University, 127# Changlexi Road, Xi'an, 710032, China
| | - Hao Sun
- Department of General Medicine, Xijing Hospital, Fourth Military Medical University, 127# Changlexi Road, Xi'an, 710032, China
| | - Meng Deng
- Department of General Medicine, Xijing Hospital, Fourth Military Medical University, 127# Changlexi Road, Xi'an, 710032, China
| | - Yufeng Qiu
- Department of General Medicine, Xijing Hospital, Fourth Military Medical University, 127# Changlexi Road, Xi'an, 710032, China
| | - Wei Yi
- Department of Cardiovascular Surgery, Xijing Hospital, Fourth Military Medical University, 127# Changlexi Road, Xi'an, 710032, China.
| | - Yang Sun
- Department of General Medicine, Xijing Hospital, Fourth Military Medical University, 127# Changlexi Road, Xi'an, 710032, China.
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Pan X, Li X, Zhang L, Wu F, Zhang Q, Xu S, Shen C, Liang J, Pan R. Umbilical cord mesenchymal stem cells relieve osteoarthritis in rats through immunoregulation and inhibition of chondrocyte apoptosis. Sci Rep 2023; 13:14975. [PMID: 37697034 PMCID: PMC10495383 DOI: 10.1038/s41598-023-42349-x] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2022] [Accepted: 09/08/2023] [Indexed: 09/13/2023] Open
Abstract
This study aims to investigate the effectiveness of umbilical cord mesenchymal stem cells (UCMSCs) in treating osteoarthritis (OA). Sprague-Dawley rats were used in in vivo experiments and divided into four groups: normal, OA model, saline, and UCMSC-treated groups (n = 6). An OA model was established by injecting iodoacetic acid into the joint cavity. The results indicate that UCMSC transplantation significantly reduced joint surface and articular cartilage damage, and the levels of IL-1β, TNF-α, and MMP13 in the joint fluid were significantly reduced after UCMSC treatment. In vitro experiments showed that co-culturing UCMSCs and chondrocytes promoted the expression of aggrecan, COL2, SOX9, and BCL-2; downregulated the expression of BAX and BAD in chondrocytes; and promoted the expression of IL-10 and TGF-β1 in UCMSCs. Additionally, the supernatant of UCMSCs inhibited the expression of IL-1β and TNF-α in the articular cavity and promoted the expression of COL2 and aggrecan in vivo. These effects were impaired when IL-10 and TGF-β1 were removed. Collectively, UCMSC transplantation appears to improve joint pathology, reduce inflammatory factors, and decrease chondrocyte apoptosis, likely through the involvement of IL-10 and TGF-β1, thus providing a potential therapeutic option for patients with OA.
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Affiliation(s)
- Xin Pan
- Institute for Cell-Based Drug Development of Zhejiang Province, S-Evans Biosciences, No. 181 Wuchang Road, Hangzhou, 311122, Zhejiang, China
- Key Laboratory of Cell-Based Drug and Applied Technology Development in Zhejiang Province, Hangzhou, China
| | - Xiongfeng Li
- Huzhou Basic and Clinical Translation of Orthopaedics Key Laboratory, Affiliated Huzhou Hospital, Huzhou, China
| | - Ling Zhang
- Institute for Cell-Based Drug Development of Zhejiang Province, S-Evans Biosciences, No. 181 Wuchang Road, Hangzhou, 311122, Zhejiang, China
- Key Laboratory of Cell-Based Drug and Applied Technology Development in Zhejiang Province, Hangzhou, China
| | - Feifei Wu
- Institute for Cell-Based Drug Development of Zhejiang Province, S-Evans Biosciences, No. 181 Wuchang Road, Hangzhou, 311122, Zhejiang, China
- Key Laboratory of Cell-Based Drug and Applied Technology Development in Zhejiang Province, Hangzhou, China
| | - Qiang Zhang
- Institute for Cell-Based Drug Development of Zhejiang Province, S-Evans Biosciences, No. 181 Wuchang Road, Hangzhou, 311122, Zhejiang, China
- Key Laboratory of Cell-Based Drug and Applied Technology Development in Zhejiang Province, Hangzhou, China
| | - Shasha Xu
- Institute for Cell-Based Drug Development of Zhejiang Province, S-Evans Biosciences, No. 181 Wuchang Road, Hangzhou, 311122, Zhejiang, China
- Key Laboratory of Cell-Based Drug and Applied Technology Development in Zhejiang Province, Hangzhou, China
| | - Chengchun Shen
- Huzhou Basic and Clinical Translation of Orthopaedics Key Laboratory, Affiliated Huzhou Hospital, Huzhou, China
| | - Jinfeng Liang
- Zhejiang Center for Drug & Cosmetic Evaluation, Hangzhou, 310012, China.
| | - Ruolang Pan
- Institute for Cell-Based Drug Development of Zhejiang Province, S-Evans Biosciences, No. 181 Wuchang Road, Hangzhou, 311122, Zhejiang, China.
- Key Laboratory of Cell-Based Drug and Applied Technology Development in Zhejiang Province, Hangzhou, China.
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Almasoudi LS, Alqasimi GJ, AlHarbi RA, Alotaibi RS, Alharbi SA. Awareness of Stem Cell Therapy for Diabetes Among Type II Diabetic Patients in Makkah: A Cross-Sectional Study. Cureus 2023; 15:e40981. [PMID: 37503474 PMCID: PMC10370506 DOI: 10.7759/cureus.40981] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/26/2023] [Indexed: 07/29/2023] Open
Abstract
Background Diabetes mellitus is a chronic disease that affects millions of people worldwide. Several studies have suggested using stem cells for diabetes treatment. However, there is a lack of research assessing the population's awareness of stem cells. This study aimed to evaluate the level of awareness regarding the use of stem cell therapy for type 2 diabetes mellitus (T2DM). Methodology This study was conducted from December 2021 to April 2022 through an online survey that was distributed electronically via social media platforms. T2DM patients or their care providers who lived in Makkah were included. Patients aged less than 18 years and those with mental disabilities were excluded. Results Of the 316 participants included in the study, 56% were males, 33% had an age range of 46-55 years, and 76% were married. T2DM patients and their caregivers had a moderate level of awareness about stem cell therapy, with caregivers having higher awareness than diabetic patients. A non-significant relationship was found between educational level, income, diabetes control, time of diagnosis, and patients' awareness. However, regarding the decision of treatment, participants aged less than 35 years were highly likely to decide to undergo stem cell treatment compared to other age groups. Conclusions There is a moderate level of awareness about stem cell therapy as a treatment option for T2DM among T2DM patients and caregivers in Makkah. Hence, there is a need to raise awareness by using online and in-person well-organized education programs in Makkah.
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Affiliation(s)
| | | | | | | | - Samah A Alharbi
- Physiology Department, Faculty of Medicine, Umm Al-Qura University, Makkah, SAU
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12
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Hu XH, Chen L, Wu H, Tang YB, Zheng QM, Wei XY, Wei Q, Huang Q, Chen J, Xu X. Cell therapy in end-stage liver disease: replace and remodel. Stem Cell Res Ther 2023; 14:141. [PMID: 37231461 DOI: 10.1186/s13287-023-03370-z] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2022] [Accepted: 04/26/2023] [Indexed: 05/27/2023] Open
Abstract
Liver disease is prevalent worldwide. When it reaches the end stage, mortality rises to 50% or more. Although liver transplantation has emerged as the most efficient treatment for end-stage liver disease, its application has been limited by the scarcity of donor livers. The lack of acceptable donor organs implies that patients are at high risk while waiting for suitable livers. In this scenario, cell therapy has emerged as a promising treatment approach. Most of the time, transplanted cells can replace host hepatocytes and remodel the hepatic microenvironment. For instance, hepatocytes derived from donor livers or stem cells colonize and proliferate in the liver, can replace host hepatocytes, and restore liver function. Other cellular therapy candidates, such as macrophages and mesenchymal stem cells, can remodel the hepatic microenvironment, thereby repairing the damaged liver. In recent years, cell therapy has transitioned from animal research to early human studies. In this review, we will discuss cell therapy in end-stage liver disease treatment, especially focusing on various cell types utilized for cell transplantation, and elucidate the processes involved. Furthermore, we will also summarize the practical obstacles of cell therapy and offer potential solutions.
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Affiliation(s)
- Xin-Hao Hu
- The Fourth School of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou, 310053, China
- Key Laboratory of Integrated Oncology and Intelligent Medicine of Zhejiang Province, Department of Hepatobiliary and Pancreatic Surgery, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou, 310006, China
| | - Lan Chen
- Zhejiang Chinese Medical University, Hangzhou, 310053, China
| | - Hao Wu
- NHC Key Laboratory of Combined Multi-Organ Transplantation, Hangzhou, 310003, China
| | - Yang-Bo Tang
- NHC Key Laboratory of Combined Multi-Organ Transplantation, Hangzhou, 310003, China
| | - Qiu-Min Zheng
- Life Sciences Institute, Zhejiang University, Hangzhou, 310058, China
| | - Xu-Yong Wei
- Key Laboratory of Integrated Oncology and Intelligent Medicine of Zhejiang Province, Department of Hepatobiliary and Pancreatic Surgery, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou, 310006, China
| | - Qiang Wei
- Key Laboratory of Integrated Oncology and Intelligent Medicine of Zhejiang Province, Department of Hepatobiliary and Pancreatic Surgery, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou, 310006, China
| | - Qi Huang
- Zhejiang Chinese Medical University, Hangzhou, 310053, China
| | - Jian Chen
- Key Laboratory of Integrated Oncology and Intelligent Medicine of Zhejiang Province, Department of Hepatobiliary and Pancreatic Surgery, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou, 310006, China.
| | - Xiao Xu
- The Fourth School of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou, 310053, China.
- Key Laboratory of Integrated Oncology and Intelligent Medicine of Zhejiang Province, Department of Hepatobiliary and Pancreatic Surgery, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou, 310006, China.
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Li Y, Liu H, Ding Y, Li W, Zhang Y, Luo S, Xiang Q. The Use of Hydrogel-Based Materials for Radioprotection. Gels 2023; 9:gels9040301. [PMID: 37102914 PMCID: PMC10137482 DOI: 10.3390/gels9040301] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2023] [Revised: 03/25/2023] [Accepted: 03/30/2023] [Indexed: 04/07/2023] Open
Abstract
Major causes of the radiation-induced disease include nuclear accidents, war-related nuclear explosions, and clinical radiotherapy. While certain radioprotective drug or bioactive compounds have been utilized to protect against radiation-induced damage in preclinical and clinical settings, these strategies are hampered by poor efficacy and limited utilization. Hydrogel-based materials are effective carriers capable of enhancing the bioavailability of compounds loaded therein. As they exhibit tunable performance and excellent biocompatibility, hydrogels represent promising tools for the design of novel radioprotective therapeutic strategies. This review provides an overview of common approaches to radioprotective hydrogel preparation, followed by a discussion of the pathogenesis of radiation-induced disease and the current states of research focused on using hydrogels to protect against these diseases. These findings ultimately provide a foundation for discussions of the challenges and future prospects associated with the use of radioprotective hydrogels.
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Affiliation(s)
- Yang Li
- Center of Emergency, First Affiliated Hospital, Third Military Medical University (Army Medical University), Chongqing 400038, China
- Institute of Combined Injury, State Key Laboratory of Trauma, Burns and Combined Injury, Chongqing Engineering Research Center for Nanomedicine, College of Preventive Medicine, Chongqing 400038, China
| | - Han Liu
- Center of Emergency, First Affiliated Hospital, Third Military Medical University (Army Medical University), Chongqing 400038, China
| | - Yaqun Ding
- Center of Emergency, First Affiliated Hospital, Third Military Medical University (Army Medical University), Chongqing 400038, China
| | - Wanyu Li
- Institute of Combined Injury, State Key Laboratory of Trauma, Burns and Combined Injury, Chongqing Engineering Research Center for Nanomedicine, College of Preventive Medicine, Chongqing 400038, China
| | - Yuansong Zhang
- Center of Emergency, First Affiliated Hospital, Third Military Medical University (Army Medical University), Chongqing 400038, China
| | - Shenglin Luo
- Institute of Combined Injury, State Key Laboratory of Trauma, Burns and Combined Injury, Chongqing Engineering Research Center for Nanomedicine, College of Preventive Medicine, Chongqing 400038, China
| | - Qiang Xiang
- Center of Emergency, First Affiliated Hospital, Third Military Medical University (Army Medical University), Chongqing 400038, China
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Safitri E, Purnobasuki H, Purnama MTE, Chhetri S. Role of apoptotic inhibitors, viability, and differentiation in low oxygen tension of mesenchymal stem cells cultured in a rat model of ovarian failure. F1000Res 2023; 12:24. [PMID: 38644927 PMCID: PMC11031646 DOI: 10.12688/f1000research.124919.1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 11/11/2022] [Indexed: 04/23/2024] Open
Abstract
Background: Stem cell therapy shows applications potential for malnutrition-induced ovarian failure in rat models. However, it is ineffective because of the lack of viability and differentiation of transplanted stem cells, resulting in low adaptation and survival rates. We aimed to determine whether stem cells cultured under low oxygen (O 2) tension improves the adaptability and viability of stem cells, as well as ovarian failure. Methods: After four days of culturing mesenchymal stem cells (MSCs) in 21% oxygen (normoxia) as the T2 group and 1% oxygen (low O 2 or hypoxia) as the T1 group, 200 million bone marrow-derived MSCs per rat were transplanted into female rats with ovarian failure (15 rats per treatment group). A total of 15 fertile and 15 infertile rats were categorized as the C+ and C- groups, respectively. Results: The slight increase in cells expressing HSP70 (C+, T2, T1, and C- groups were 0.5 a±0.53, 1.7 a±0.82, 6.2 b±1.5, and 9.6 c±1.3, respectively), decrease in cells expressing caspase-3 as an apoptotic inhibitor (C+, T2, T1, and C- groups were 0.2 a±0.42, 0.6 a±0.52, 4.8 b±1.03, and 7.3 c±1.42, respectively), and increase in cells expressing VEGF-1 (C+, T2, T1, and C- groups were 10.8 c±1.55, 8.7 b±0.48, 0.4 a±0.52, and 0.2 a±0.42, respectively) and GDF-9 (C+, T2, T1, and C- groups were 5.8 c±1.47, 4.6 b±0.97, 0.5 a±0.53, and 0.3 a±0.48, respectively) were used as markers for viability and differentiation in ovarian tissue, indicating that MSCs cultured under low O 2 tension were more effective than those cultured under normoxic conditions as a treatment for female rats with ovarian failure. Furthermore, infertile female rats treated with MSCs cultivated under low O 2 tension had an enhanced ovarian tissue shape, as indicated by the increasing Graafian follicle count (C+, T2, T1, and C- groups were 8.9 c±0.74, 4.5 b±0.71, 0.5 a±0.53, and 0.4 a±0.52, respectively). Conclusions: MSCs cultured under low O 2 tension are an effective treatment for malnourished rats with ovarian failure.
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Affiliation(s)
- Erma Safitri
- Division of Veterinary Reproduction, Department of Veterinary Science, Faculty of Veterinary Medicine, Universitas Airlangga, Surabaya, East Java, 60115, Indonesia
| | - Hery Purnobasuki
- Department of Biology, Faculty of Science and Technology, Universitas Airlangga, Surabaya, East Java, 60115, Indonesia
| | - Muhammad Thohawi Elziyad Purnama
- Division of Veterinary Anatomy, Department of Veterinary Science, Faculty of Veterinary Medicine, Universitas Airlangga, Surabaya, East Java, 60115, Indonesia
| | - Shekhar Chhetri
- Department of Animal Science, College of Natural Resources, Royal University of Bhutan, Lobesa, Punakha, 13001, Bhutan
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15
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Anwar I, Ashfaq UA. Impact of Nanotechnology on Differentiation and Augmentation of Stem Cells for Liver Therapy. Crit Rev Ther Drug Carrier Syst 2023; 40:89-116. [PMID: 37585310 DOI: 10.1615/critrevtherdrugcarriersyst.2023042400] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/18/2023]
Abstract
The liver is one of the crucial organs of the body that performs hundreds of chemical reactions needed by the body to survive. It is also the largest gland of the body. The liver has multiple functions, including the synthesis of chemicals, metabolism of nutrients, and removal of toxins. It also acts as a storage unit. The liver has a unique ability to regenerate itself, but it can lead to permanent damage if the injury is beyond recovery. The only possible treatment of severe liver damage is liver transplant which is a costly procedure and has several other drawbacks. Therefore, attention has been shifted towards the use of stem cells that have shown the ability to differentiate into hepatocytes. Among the numerous kinds of stem cells (SCs), the mesenchymal stem cells (MSCs) are the most famous. Various studies suggest that an MSC transplant can repair liver function, improve the signs and symptoms, and increase the chances of survival. This review discusses the impact of combining stem cell therapy with nanotechnology. By integrating stem cell science and nanotechnology, the information about stem cell differentiation and regulation will increase, resulting in a better comprehension of stem cell-based treatment strategies. The augmentation of SCs with nanoparticles has been shown to boost the effect of stem cell-based therapy. Also, the function of green nanoparticles in liver therapies is discussed.
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Affiliation(s)
- Ifrah Anwar
- Department of Bioinformatics and Biotechnology, Government College University Faisalabad, Faisalabad, Pakistan
| | - Usman Ali Ashfaq
- Department of Bioinformatics and Biotechnology, Government College University Faisalabad, Faisalabad, Pakistan
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16
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Liang F, Luo YF, Guo Z, Qian Q, Meng XB, Mo ZH. MicroRNA-139-5p mediates BMSCs impairment in diabetes by targeting HOXA9/c-Fos. FASEB J 2023; 37:e22697. [PMID: 36527387 DOI: 10.1096/fj.202201059r] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/2022] [Revised: 10/13/2022] [Accepted: 11/28/2022] [Indexed: 12/23/2022]
Abstract
The properties and functions of BMSCs were altered by the diabetic microenvironment, and its mechanism was not very clear. In recent years, the regulation of the function of BMSCs by microRNA has become a research hotspot, meanwhile, HOX genes also have been focused on and involved in multiple functions of stem cells. In this study, we investigated the role of miR-139-5p in diabetes-induced BMSC impairment. Since HOXA9 may be a target gene of miR-139-5p, we speculated that miR-139-5p/HOXA9 might be involved in regulating the biological characteristics and the function of BMSCs in diabetes. We demonstrated that the miR-139-5p expression was increased in BMSCs derived from STZ-induced diabetic rats. MiR-139-5p mimics were able to inhibit cell proliferation, and migration and promoted senescence and apoptosis in vitro. MiR-139-5p induced the down-regulated expression of HOXA9 and c-Fos in BMSCs derived from normal rats. Moreover, miR-139-5p inhibitors reversed the tendency in diabetic-derived BMSCs. Further, gain-and-loss function experiments indicated that miR-139-5p regulated the functions of BMSCs by targeting HOXA9 and c-Fos. In vivo wound model experiments showed that the downregulation of miR-139-5p further promoted the epithelialization and angiogenesis of diabetic BMSC-mediated skin. In conclusion, induction of miR-139-5p upregulation mediated the impairment of BMSCs through the HOXA9/c-Fos pathway in diabetic rats. Therefore, miR-139-5p/HOXA9 might be an important therapeutic target in treating diabetic BMSCs and diabetic complications in the future.
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Affiliation(s)
- Fang Liang
- Department of Endocrinology, Third Xiangya Hospital of Central South University and Diabetic Foot Research Center of Central South University, Changsha, China
| | - Yu-Fang Luo
- Department of Endocrinology, Third Xiangya Hospital of Central South University and Diabetic Foot Research Center of Central South University, Changsha, China
| | - Zi Guo
- Department of Endocrinology, Third Xiangya Hospital of Central South University and Diabetic Foot Research Center of Central South University, Changsha, China
| | - Qiang Qian
- Department of Endocrinology, Third Xiangya Hospital of Central South University and Diabetic Foot Research Center of Central South University, Changsha, China
| | - Xu-Biao Meng
- Department of Endocrinology, Haikou People's Hospital & Haikou Affiliated Hospital of Central South University Xiangya School of Medicine, Haikou, China
| | - Zhao-Hui Mo
- Department of Endocrinology, Third Xiangya Hospital of Central South University and Diabetic Foot Research Center of Central South University, Changsha, China
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17
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Garcia G, Oliveira R, Dariolli R, Rudge M, Barbosa A, Floriano J, Ribeiro-Paes J. Isolation and characterization of farm pig adipose tissue-derived mesenchymal stromal/stem cells. Braz J Med Biol Res 2022; 55:e12343. [PMID: 36477953 PMCID: PMC9728630 DOI: 10.1590/1414-431x2022e12343] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/28/2022] [Accepted: 10/17/2022] [Indexed: 12/03/2022] Open
Abstract
Adipose tissue-derived mesenchymal stromal/stem cells (ASCs) are considered important tools in regenerative medicine and are being tested in several clinical studies. Porcine models are frequently used to obtain adipose tissue, due to the abundance of material and because they have immunological and physiological similarities with humans. However, it is essential to understand the effects and safe application of ASCs from pigs (pASCs) as an alternative therapy for diseases. Although minipigs are easy-to-handle animals that require less food and space, acquiring and maintaining them in a bioterium can be costly. Thus, we present a protocol for the isolation and proliferation of ASCs isolated from adipose tissue of farm pigs. Adipose tissue samples were extracted from the abdominal region of the animals. Because the pigs were not raised in a controlled environment, such as a bioterium, it was necessary to carry out rigorous procedures for disinfection. After this procedure, cells were isolated by mechanical dissociation and enzymatic digestion. A proliferation curve was performed and used to calculate the doubling time of the population. The characterization of pASCs was performed by immunophenotyping and cell differentiation in osteogenic and adipogenic lineages. The described method was efficient for the isolation and cultivation of pASCs, maintaining cellular attributes, such as surface antigens and multipotential differentiation during in vitro proliferation. This protocol presents the isolation and cultivation of ASCs from farm pig as an alternative for the isolation and cultivation of ASCs from minipigs, which require strictly controlled maintenance conditions and a more expensive process.
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Affiliation(s)
- G.A. Garcia
- Departamento de Biotecnologia, Faculdade de Ciências e Letras, Universidade Estadual Paulista, Assis, SP, Brasil
| | - R.G. Oliveira
- Departamento de Biotecnologia, Faculdade de Ciências e Letras, Universidade Estadual Paulista, Assis, SP, Brasil,Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo, SP, Brasil
| | - R. Dariolli
- Laboratório de Genética e Cardiologia Molecular, Instituto do Coração, São Paulo, SP, Brasil,Department of Pharmacological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - M.V.C. Rudge
- Departamento de Ginecologia e Obstetrícia, Faculdade de Medicina, Universidade Estadual Paulista, Botucatu, SP, Brasil
| | - A.M.P. Barbosa
- Departamento de Fisioterapia e Terapia Ocupacional, Faculdade de Filosofia e Ciências, Universidade Estadual Paulista, Marília, SP, Brasil
| | - J.F. Floriano
- Departamento de Ginecologia e Obstetrícia, Faculdade de Medicina, Universidade Estadual Paulista, Botucatu, SP, Brasil
| | - J.T. Ribeiro-Paes
- Departamento de Biotecnologia, Faculdade de Ciências e Letras, Universidade Estadual Paulista, Assis, SP, Brasil,Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo, SP, Brasil
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18
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Zhu L, Wang S, Qu J, Hui Z, Kan C, Hou N, Sun X. The Therapeutic Potential of Mesenchymal Stem Cells in the Treatment of Diabetes Mellitus. Cell Reprogram 2022; 24:329-342. [PMID: 35877064 DOI: 10.1089/cell.2022.0039] [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] [Indexed: 01/25/2023] Open
Abstract
Mesenchymal stem cells (MSCs) exist in many tissues and can differentiate into cells of multiple lineages, such as adipocytes, osteoblasts, or chondrocytes. MSC administration has demonstrated therapeutic potential in various degenerative and inflammatory diseases (e.g., graft-vs.-host disease, multiple sclerosis, Crohn's disease, organ fibrosis, and diabetes mellitus [DM]). The mechanisms involved in the therapeutic effects of MSCs are multifaceted. Generally, implanted MSCs can migrate to sites of injury, where they establish an anti-inflammatory and regenerative microenvironment in damaged tissues. In addition, MSCs can modulate innate and adaptive immune responses through immunosuppressive mechanisms that involve immune cells, inflammatory cytokines, chemokines, and immunomodulatory factors. DM has a high prevalence worldwide; it also contributes to a high rate of mortality worldwide. MSCs offer a promising therapeutic agent to prevent or repair damage from DM and diabetic complications through properties such as multilineage differentiation, homing, promotion of angiogenesis, and immunomodulation (e.g., prevention of oxidative stress, fibrosis, and cell death). In this study, we review current findings regarding the immunomodulatory and regenerative mechanisms of MSCs, as well as their therapeutic applications in DM and DM-related complications.
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Affiliation(s)
- Liang Zhu
- Department of Endocrinology and Metabolism, Affiliated Hospital of Weifang Medical University, Weifang, China
- Clinical Research Center, Affiliated Hospital of Weifang Medical University, Weifang, China
| | - Sheng Wang
- Department of Spinal Surgery, Affiliated Hospital of Weifang Medical University, Weifang, China
| | - JunSheng Qu
- Department of Endocrinology and Metabolism, Affiliated Hospital of Weifang Medical University, Weifang, China
- Clinical Research Center, Affiliated Hospital of Weifang Medical University, Weifang, China
| | - Zongguang Hui
- Department of Endocrinology and Metabolism, Affiliated Hospital of Weifang Medical University, Weifang, China
- Clinical Research Center, Affiliated Hospital of Weifang Medical University, Weifang, China
| | - Chengxia Kan
- Department of Endocrinology and Metabolism, Affiliated Hospital of Weifang Medical University, Weifang, China
- Clinical Research Center, Affiliated Hospital of Weifang Medical University, Weifang, China
| | - Ningning Hou
- Department of Endocrinology and Metabolism, Affiliated Hospital of Weifang Medical University, Weifang, China
- Clinical Research Center, Affiliated Hospital of Weifang Medical University, Weifang, China
| | - Xiaodong Sun
- Department of Endocrinology and Metabolism, Affiliated Hospital of Weifang Medical University, Weifang, China
- Clinical Research Center, Affiliated Hospital of Weifang Medical University, Weifang, China
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Almalki SG. Adipose-derived mesenchymal stem cells and wound healing: Potential clinical applications in wound repair. Saudi Med J 2022; 43:1075-1086. [PMID: 36261194 PMCID: PMC9994497 DOI: 10.15537/smj.2022.43.10.20220522] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/21/2022] [Accepted: 09/06/2022] [Indexed: 06/16/2023] Open
Abstract
Delayed and chronic wounds result from the dysregulation of molecular and cellular events associated with wound healing, including migration, inflammation, angiogenesis, extracellular matrix (ECM) remodeling, and re-epithelialization. Adipose tissue is an abundant, easily accessible, and rich source of mesenchymal stem cells (MSCs) with high therapeutic potential. In addition to their capability to differentiate into various lineages with specialized functions, adipose-derived MSCs (AMSCs) can mediate to the wound repair process through the secretion of different growth factors and mediators rather than making structural contribution alone. Adipose-derived MSCs mediate the formation of blood vessels, recruit progenitor cells, stimulate cell differentiation and ECM formation, and promote wound healing by releasing immune mediators and exosomes. Herein, we discuss and review the therapeutic potential of AMSCs for wound repair via acceleration of wound closure, re-epithelialization, enhancement of angiogenesis and immunomodulation of prolonged inflammatory responses, as well as the current challenges in clinical implementation.
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Affiliation(s)
- Sami G. Almalki
- From the Department of Medical Laboratory Sciences, College of Applied Medical Sciences, Majmaah University, Majmaah, Kingdom of Saudi Arabia
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20
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Gao S, Zhang Y, Liang K, Bi R, Du Y. Mesenchymal Stem Cells (MSCs): A Novel Therapy for Type 2 Diabetes. Stem Cells Int 2022; 2022:8637493. [PMID: 36045953 PMCID: PMC9424025 DOI: 10.1155/2022/8637493] [Citation(s) in RCA: 17] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2021] [Revised: 02/15/2022] [Accepted: 07/05/2022] [Indexed: 11/25/2022] Open
Abstract
Although plenty of drugs are currently available for type 2 diabetes mellitus (T2DM), a subset of patients still failed to restore normoglycemia. Recent studies proved that symptoms of T2DM patients who are unresponsive to conventional medications could be relieved with mesenchymal stem/stromal cell (MSC) therapy. However, the lack of systematic summary and analysis for animal and clinical studies of T2DM has limited the establishment of standard guidelines in anti-T2DM MSC therapy. Besides, the therapeutic mechanisms of MSCs to combat T2DM have not been thoroughly understood. In this review, we present an overview of the current status of MSC therapy in treating T2DM for both animal studies and clinical studies. Potential mechanisms of MSC-based intervention on multiple pathological processes of T2DM, such as β-cell exhaustion, hepatic dysfunction, insulin resistance, and systemic inflammation, are also delineated. Moreover, we highlight the importance of understanding the pharmacokinetics (PK) of transplanted cells and discuss the hurdles in MSC-based T2DM therapy toward future clinical applications.
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Affiliation(s)
- Shuang Gao
- Department of Biomedical Engineering, School of Medicine, Tsinghua-Peking Center for Life Sciences, Tsinghua University, Beijing 100084, China
| | - Yuanyuan Zhang
- Department of Biomedical Engineering, School of Medicine, Tsinghua-Peking Center for Life Sciences, Tsinghua University, Beijing 100084, China
| | - Kaini Liang
- Department of Biomedical Engineering, School of Medicine, Tsinghua-Peking Center for Life Sciences, Tsinghua University, Beijing 100084, China
| | - Ran Bi
- Department of Biomedical Engineering, School of Medicine, Tsinghua-Peking Center for Life Sciences, Tsinghua University, Beijing 100084, China
| | - Yanan Du
- Department of Biomedical Engineering, School of Medicine, Tsinghua-Peking Center for Life Sciences, Tsinghua University, Beijing 100084, China
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21
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Su W, Yu S, Yin Y, Li B, Xue J, Wang J, Gu Y, Zhang H, Lyu Z, Mu Y, Cheng Y. Diabetic microenvironment preconditioning of adipose tissue-derived mesenchymal stem cells enhances their anti-diabetic, anti-long-term complications, and anti-inflammatory effects in type 2 diabetic rats. STEM CELL RESEARCH & THERAPY 2022; 13:422. [PMID: 35986406 PMCID: PMC9389728 DOI: 10.1186/s13287-022-03114-5] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/09/2022] [Accepted: 08/04/2022] [Indexed: 11/25/2022]
Abstract
Background Mesenchymal stem cells (MSCs) exert anti-diabetic effects and improve long-term complications via secretory effects that regulate macrophage polarisation and attenuate inflammation. Enhancing the efficacy of MSCs needs to be explored further. The in vitro culture microenvironment influences the secretory profile of MSCs. Therefore, we hypothesised that a diabetic microenvironment would promote the secretion of cytokines responsible for macrophage polarisation, further attenuating systemic inflammation and enhancing the effects of MSCs on type 2 diabetes (T2D) and long-term diabetic complications. Methods Preconditioned adipose-derived mesenchymal stem cells (pre-ADSCs) were obtained after co-cultivating ADSCs in a diabetic metabolic environment (including high sugar, advanced glycation end-product, and lipopolysaccharides). The regulatory effects of pre-ADSCs on macrophages were observed in vitro. A T2D rat model was induced with a high-fat diet for 32 weeks combined with an intraperitoneal injection of streptozotocin. Sprague–Dawley (SD) rats were divided into four groups: normal group, diabetes without treatment group (PBS), ADSC treatment group, and pre-ADSC treatment group. ADSCs and pre-ADSCs were intravenously administered weekly to SD rats for 6 months, and then glucose homeostasis and long-term diabetic complications were evaluated in each group. Results The secretion of cytokines related to M2 macrophage polarisation (IL-6, MCP-1, etc.) was increased in the pre-ADSC group in the in vitro model. Pre-ADSC treatment significantly maintained blood glucose homeostasis, reduced insulin resistance, promoted islet regeneration, and ameliorated the complications related to diabetes in rats (chronic kidney disease, non-alcoholic steatohepatitis, lung fibrosis, and cataract) compared to the ADSC group (P < 0.05). Additionally, the number of anti-inflammatory M2 macrophage phenotypes was enhanced in tissues following pre-ADSC injections. Moreover, the expression of pro-inflammatory genes (iNOS, TNF-α, IL-1β) was reduced whereas that of anti-inflammatory genes (Arg1, CD206, and Il-10) was increased after cultivation with pre-ADSCs. Conclusion Diabetic microenvironment-preconditioned ADSCs effectively strengthen the capacity against inflammation and modulate the progress of long-term T2D complications. Supplementary Information The online version contains supplementary material available at 10.1186/s13287-022-03114-5.
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Ahmed HH, Aglan HA, Beherei HH, Mabrouk M, Mahmoud NS. The promising role of hypoxia-resistant insulin-producing cells in ameliorating diabetes mellitus in vivo. Future Sci OA 2022; 8:FSO811. [PMID: 36248064 PMCID: PMC9540411 DOI: 10.2144/fsoa-2022-0005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/19/2022] [Accepted: 08/25/2022] [Indexed: 11/23/2022] Open
Abstract
AIM This study aimed to evaluate the efficacy of hypoxia-persistent insulin-producing cells (IPCs) against diabetes in vivo. MATERIALS & METHODS Mesenchymal stem cells (MSCs) differentiation into IPCs in the presence of Se/Ti (III) or CeO2 nanomaterials. IPCs were subjected to hypoxia and hypoxia genes were analyzed. PKH-26-labeled IPCs were infused in diabetic rats to evaluate their anti-diabetic potential. RESULTS MSCs were differentiated into functional IPCs. IPCs exhibited overexpression of anti-apoptotic genes and down-expression of hypoxia and apoptotic genes. IPCs implantation elicited glucose depletion and elevated insulin, HK and G6PD levels. They provoked VEGF and PDX-1 upregulation and HIF-1α and Caspase-3 down-regulation. IPCs transplantation ameliorated the destabilization of pancreatic tissue architecture. CONCLUSION The chosen nanomaterials were impressive in generating hypoxia-resistant IPCs that could be an inspirational strategy for curing diabetes.
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Affiliation(s)
- Hanaa H Ahmed
- Hormones Department, Medical Research & Clinical Studies Institute, National Research Centre, Giza, 12622, Egypt
- Stem Cells Lab, Center of Excellence for Advanced Sciences, National Research Centre, Giza, 12622, Egypt
| | - Hadeer A Aglan
- Hormones Department, Medical Research & Clinical Studies Institute, National Research Centre, Giza, 12622, Egypt
- Stem Cells Lab, Center of Excellence for Advanced Sciences, National Research Centre, Giza, 12622, Egypt
| | - Hanan H Beherei
- Refractories, Ceramics & Building Materials Department, Advanced Materials Technology & Mineral Resources Research Institute, National Research Centre, Giza, 12622, Egypt
| | - Mostafa Mabrouk
- Refractories, Ceramics & Building Materials Department, Advanced Materials Technology & Mineral Resources Research Institute, National Research Centre, Giza, 12622, Egypt
| | - Nadia S Mahmoud
- Hormones Department, Medical Research & Clinical Studies Institute, National Research Centre, Giza, 12622, Egypt
- Stem Cells Lab, Center of Excellence for Advanced Sciences, National Research Centre, Giza, 12622, Egypt
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23
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Rafiee Z, Orazizadeh M, Nejad Dehbashi F, Neisi N, Babaahmadi-Rezaei H, Mansouri E. Mesenchymal stem cells derived from the kidney can ameliorate diabetic nephropathy through the TGF-β/Smad signaling pathway. ENVIRONMENTAL SCIENCE AND POLLUTION RESEARCH INTERNATIONAL 2022; 29:53212-53224. [PMID: 35278177 DOI: 10.1007/s11356-021-17954-w] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/11/2021] [Accepted: 12/01/2021] [Indexed: 06/14/2023]
Abstract
Diabetic nephropathy (DN) has been introduced as one of the main microvascular complications in diabetic patients, the most common cause of end-stage renal disease (ESRD). Based on the therapeutic potential of mesenchymal stem cells in tissue repair, we aimed to test the hypothesis that kidney stem cells (KSCs) might be effective in the kidney regeneration process. Stem cells from rat kidney were separated, and the surface stem cell markers were determined by flow cytometry analysis. Thirty-two Sprague Dawley rats were divided into four groups (control, control that received kidney stem cells, diabetic, diabetic treated with stem cells). To establish diabetic, model STZ (streptozotocin) (60 mg/kg) was used. The KSCs were injected into experimental groups via tail vein (2 × 106 cells/rat). In order to determine the impact of stem cells on the function and structure of the kidney, biochemical and histological parameters were measured. Further, the expression of miRNA-29a, miR-192, IL-1β, and TGF-β was determined through the real-time PCR technique. Phosphorylation of Smad2/3 was evaluated by using the standard western blotting. The KSCs significantly reduced blood nitrogen (BUN), serum creatinine (Scr), and 24-h urinary proteins in DN (P < 0.05). IL-1β and TGF-β significantly increased in the kidney of diabetic rats. In addition, the expression of miR-29a is significantly increased, whereas miR-192 decreased after treatment with KSCs (P < 0.05). Diabetic rats showed an increased level of phosphorylation of both Smad2 and Smad3 (P < 0.05). Periodic acid-Schiff (PAS) staining showed improved histopathological changes in the presence of KSCs. Stem cells derived from adult rat kidney may be an option for treating the early DN to improve the functions and structure of kidneys in rats with DN.
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Affiliation(s)
- Zeinab Rafiee
- Medical Basic Sciences Research Institute, Cellular and Molecular Research Center, Department of Anatomical Sciences, Faculty of Medicine, Ahvaz Jundishapur University of Medical Sciences, 61335, Ahvaz, Iran
| | - Mahmoud Orazizadeh
- Medical Basic Sciences Research Institute, Cellular and Molecular Research Center, Department of Anatomical Sciences, Faculty of Medicine, Ahvaz Jundishapur University of Medical Sciences, 61335, Ahvaz, Iran
| | - Fereshteh Nejad Dehbashi
- Medical Basic Sciences Research Institute, Cellular and Molecular Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | - Niloofar Neisi
- Alimentary Tract Research Center, Imam Khomeini Hospital Clinical Research Development Unit, Infectious and Tropical Diseases Research Center, Department of Virology, the School of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | - Hossein Babaahmadi-Rezaei
- Hyperlipidemia Research Center, Department of Clinical Biochemistry, Faculty of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | - Esrafil Mansouri
- Medical Basic Sciences Research Institute, Cellular and Molecular Research Center, Department of Anatomical Sciences, Faculty of Medicine, Ahvaz Jundishapur University of Medical Sciences, 61335, Ahvaz, Iran.
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24
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Zhu Y, Luo M, Bai X, Lou Y, Nie P, Jiang S, Li J, Li B, Luo P. Administration of mesenchymal stem cells in diabetic kidney disease: mechanisms, signaling pathways, and preclinical evidence. Mol Cell Biochem 2022; 477:2073-2092. [PMID: 35469057 DOI: 10.1007/s11010-022-04421-4] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2021] [Accepted: 03/22/2022] [Indexed: 02/07/2023]
Abstract
Diabetic kidney disease (DKD) is a serious microvascular complication of diabetes. Currently, the prevalence and mortality of DKD are increasing annually. However, with no effective drugs to prevent its occurrence and development, the primary therapeutic option is to control blood sugar and blood pressure. Therefore, new and effective drugs/methods are imperative to prevent the development of DKD in patients with diabetes. Mesenchymal stem cells (MSCs) with multi-differentiation potential and paracrine function have received extensive attention as a new treatment option for DKD. However, their role and mechanism in the treatment of DKD remain unclear, and clinical applications are still being explored. Given this, we here provide an unbiased review of recent advances in MSCs for the treatment of DKD in the last decade from the perspectives of the pathogenesis of DKD, biological characteristics of MSCs, and different molecular and signaling pathways. Furthermore, we summarize information on combination therapy strategies using MSCs. Finally, we discuss the challenges and prospects for clinical application.
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Affiliation(s)
- Yuexin Zhu
- Department of Nephrology, The Second Hospital of Jilin University, 218 ZiQiang Street, Changchun, 130041, Jilin, People's Republic of China
| | - Manyu Luo
- Department of Nephrology, The Second Hospital of Jilin University, 218 ZiQiang Street, Changchun, 130041, Jilin, People's Republic of China
| | - Xue Bai
- Department of Nephrology, The Second Hospital of Jilin University, 218 ZiQiang Street, Changchun, 130041, Jilin, People's Republic of China
| | - Yan Lou
- Department of Nephrology, The Second Hospital of Jilin University, 218 ZiQiang Street, Changchun, 130041, Jilin, People's Republic of China
| | - Ping Nie
- Department of Nephrology, The Second Hospital of Jilin University, 218 ZiQiang Street, Changchun, 130041, Jilin, People's Republic of China
| | - Shan Jiang
- Department of Nephrology, The Second Hospital of Jilin University, 218 ZiQiang Street, Changchun, 130041, Jilin, People's Republic of China
| | - Jicui Li
- Department of Nephrology, The Second Hospital of Jilin University, 218 ZiQiang Street, Changchun, 130041, Jilin, People's Republic of China
| | - Bing Li
- Department of Nephrology, The Second Hospital of Jilin University, 218 ZiQiang Street, Changchun, 130041, Jilin, People's Republic of China.
| | - Ping Luo
- Department of Nephrology, The Second Hospital of Jilin University, 218 ZiQiang Street, Changchun, 130041, Jilin, People's Republic of China.
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25
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Ishida Y, Nosaka M, Kondo T. Bone Marrow-Derived Cells and Wound Age Estimation. Front Med (Lausanne) 2022; 9:822572. [PMID: 35155503 PMCID: PMC8828650 DOI: 10.3389/fmed.2022.822572] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2021] [Accepted: 01/03/2022] [Indexed: 12/20/2022] Open
Abstract
Appropriate technology as well as specific target cells and molecules are key factors for determination of wound vitality or wound age in forensic practice. Wound examination is one of the most important tasks for forensic pathologists and is indispensable to distinguish antemortem wounds from postmortem damage. For vital wounds, estimating the age of the wound is also essential in determining how the wound is associated with the cause of death. We investigated bone marrow-derived cells as promising markers and their potential usefulness in forensic applications. Although examination of a single marker cannot provide high reliability and objectivity in estimating wound age, evaluating the appearance combination of bone marrow-derived cells and the other markers may allow for a more objective and accurate estimation of wound age.
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Affiliation(s)
- Yuko Ishida
- *Correspondence: Yuko Ishida ; orcid.org/0000-0001-6104-7599
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26
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Lokman Hakim NYDB, Noble S, Thomas NV, Geegana Gamage BS, Maxwell GK, Govindasamy V, Then KY, Das AK, Cheong SK. Genetic Modification as a New Approach to Ameliorate the Therapeutic Efficacy of Stem Cells in Diabetic Retinopathy. Eur J Ophthalmol 2022; 32:11206721211073430. [PMID: 35037488 DOI: 10.1177/11206721211073430] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Abstract
Over the last decades, the strategy of using stem cells has gained a lot of attention in treating many diseases. Recently, DR was identified as one of the common complications experienced by diabetic patients around the world. The current treatment strategy needs to be addressed since the active progression of DR may lead to permanent blindness. Interestingly, varieties of stem cells have emerged to optimize the therapeutic effects. It is also known that stem cells possess multilineage properties and are capable of differentiating, expanding in vitro and undergoing genetic modification. Moreover, modified stem cells have shown to be an ideal resource to prevent the degenerative disease and exhibit promising effects in conferring the migratory, anti-apoptotic, anti-inflammatory and provide better homing for cells into the damaged tissue or organ as well promoting healing properties. Therefore, the understanding of the functional properties of the stem cells may provide the comprehensive guidance to understand the manipulation of stem cells making them useful for long-term therapeutic applications. Hence in this review the potential use and current challenges of genetically modified stem cells to treat DR will be discussed along with its future perspectives.
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Affiliation(s)
| | - Steven Noble
- CryoCord Sdn Bhd, Bio-X Centre, Cyberjaya, Selangor, Malaysia
| | | | | | | | | | - Kong-Yong Then
- CryoCord Sdn Bhd, Bio-X Centre, Cyberjaya, Selangor, Malaysia
- Brighton Healthcare (Bio-X Healthcare Sdn Bhd), Bio-X Centre, Cyberjaya, Selangor, Malaysia
| | - Anjan Kumar Das
- Department of Surgery, 483702IQ City Medical College, Durgapur, West Bengal, India
| | - Soon-Keng Cheong
- Faculty of Medicine & Health Sciences, 65287Universiti Tunku Abdul Rahman (UTAR), Kajang, Selangor, Malaysia
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27
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Li B, Cheng X, Aierken A, Du J, He W, Zhang M, Tan N, Kou Z, Peng S, Jia W, Tang H, Hua J. Melatonin Promotes the Therapeutic Effect of Mesenchymal Stem Cells on Type 2 Diabetes Mellitus by Regulating TGF-β Pathway. Front Cell Dev Biol 2021; 9:722365. [PMID: 34722505 PMCID: PMC8554153 DOI: 10.3389/fcell.2021.722365] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2021] [Accepted: 09/27/2021] [Indexed: 12/26/2022] Open
Abstract
Abundant evidence proves the therapeutic effect of adipose-derived mesenchymal stem cells (ADMSCs) in the treatment of diabetes mellitus. However, the problems have not been solved that viability of ADMSCs were inconsistent and the cells quickly undergo senescence after in vitro cell culture. In addition, the therapeutic effect of ADMSCs is still not satisfactory. In this study, melatonin (MLT) was added to canine ADMSC culture medium, and the treated cells were used to treat type 2 diabetes mellitus (T2DM). Our research reveals that adding MLT to ADMSC culture medium can promote the viability of ADMSCs. This effect depends on the binding of MLT and MLT receptors, which activates the transforming growth factor β (TGF-β) pathway and then changes the cell cycle of ADMSCs and improves the viability of ADMSCs. Since ADMSCs were found to be used to treat T2DM by anti-inflammatory and anti-endoplasmic reticulum (ER) stress capabilities, our data demonstrate that MLT augment several effects of ADMSCs in remission hyperglycemia, insulin resistance, and liver glycogen metabolism in T2DM patients. This suggest that ADMSCs and MLT-ADMSCs is safe and vabulable for pet clinic.
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Affiliation(s)
- Balun Li
- Shaanxi Centre of Stem Cells Engineering and Technology, College of Veterinary Medicine, Northwest A&F University, Xianyang, China
| | - Xuedi Cheng
- Shaanxi Centre of Stem Cells Engineering and Technology, College of Veterinary Medicine, Northwest A&F University, Xianyang, China
| | - Aili Aierken
- Shaanxi Centre of Stem Cells Engineering and Technology, College of Veterinary Medicine, Northwest A&F University, Xianyang, China
| | - Jiaxin Du
- Department of Animal Engineering, Yangling Vocational and Technical College, Xianyang, China.,Department of Veterinary Medicine, College of Animal Sciences, Institute of Preventive Veterinary Sciences, Zhejiang University, Hangzhou, China
| | - Wenlai He
- Shaanxi Centre of Stem Cells Engineering and Technology, College of Veterinary Medicine, Northwest A&F University, Xianyang, China
| | - Mengfei Zhang
- Shaanxi Centre of Stem Cells Engineering and Technology, College of Veterinary Medicine, Northwest A&F University, Xianyang, China
| | - Ning Tan
- Shaanxi Centre of Stem Cells Engineering and Technology, College of Veterinary Medicine, Northwest A&F University, Xianyang, China
| | - Zheng Kou
- Shaanxi Centre of Stem Cells Engineering and Technology, College of Veterinary Medicine, Northwest A&F University, Xianyang, China
| | - Sha Peng
- Shaanxi Centre of Stem Cells Engineering and Technology, College of Veterinary Medicine, Northwest A&F University, Xianyang, China
| | - Wenwen Jia
- Shanghai East Hospital, East Hospital Affiliated to Tongji University, Shanghai, China
| | - Haiyang Tang
- Shaanxi Centre of Stem Cells Engineering and Technology, College of Veterinary Medicine, Northwest A&F University, Xianyang, China
| | - Jinlian Hua
- Shaanxi Centre of Stem Cells Engineering and Technology, College of Veterinary Medicine, Northwest A&F University, Xianyang, China
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28
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Zhu CH, Zhang DH, Zhu CW, Xu J, Guo CL, Wu XG, Cao QL, Di GH. Adult stem cell transplantation combined with conventional therapy for the treatment of end-stage liver disease: a systematic review and meta-analysis. Stem Cell Res Ther 2021; 12:558. [PMID: 34717737 PMCID: PMC8557537 DOI: 10.1186/s13287-021-02625-x] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2021] [Accepted: 10/11/2021] [Indexed: 01/11/2023] Open
Abstract
End-stage liver disease (ESLD) is characterized by the deterioration of liver function and a subsequent high mortality rate. Studies have investigated the use of adult stem cells to treat ESLD. Here, a systematic review and meta-analysis was conducted to determine the efficacy of a combination therapy with adult stem cell transplantation and traditional medicine for treating ESLD. Four databases-including PubMed, Web of Science, Embase, and Cochrane Library-were investigated for studies published before January 31, 2021. The main outcome indicators were liver function index, model for end-stage liver disease (MELD) scores, and Child‒Turcotte‒Pugh (CTP) scores. Altogether, 1604 articles were retrieved, of which eight met the eligibility criteria; these studies included data for 579 patients with ESLD. Combination of adult stem cell transplantation with conventional medicine significantly improved its efficacy with respect to liver function index, CTP and MELD scores, but this effect gradually decreased over time. Moreover, a single injection of stem cells was more effective than two injections with respect to MELD and CTP scores and total bilirubin (TBIL) and albumin (ALB) levels, with no significant difference in aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels. With respect to the TBIL levels, patients receiving mononuclear cells (MNCs) experienced a significantly greater therapeutic effect-starting from twenty-four weeks after the treatment-whereas with respect to ALB levels, CD34+ autologous peripheral blood stem cells (CD34+ APBSCs) and MNCs had similar therapeutic effects. Severe complications associated with adult stem cell treatment were not observed. Although the benefits of combination therapy with respect to improving liver function were slightly better than those of the traditional treatment alone, they gradually decreased over time.Systematic review registration: PROSPERO registration number: CRD42021238576.
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Affiliation(s)
- Chen-Hui Zhu
- School of Basic Medicine, Qingdao University, 308 Ningxia Road, Qingdao, 266071, China
| | - Dian-Han Zhang
- School of Basic Medicine, Qingdao University, 308 Ningxia Road, Qingdao, 266071, China
| | - Chen-Wei Zhu
- School of Basic Medicine, Qingdao University, 308 Ningxia Road, Qingdao, 266071, China
| | - Jing Xu
- School of Basic Medicine, Qingdao University, 308 Ningxia Road, Qingdao, 266071, China
| | - Chuan-Long Guo
- College of Chemical Engineering, Qingdao University of Science and Technology, Qingdao, China
| | - Xiang-Gen Wu
- College of Chemical Engineering, Qingdao University of Science and Technology, Qingdao, China
| | - Qi-Long Cao
- Qingdao Haier Biotech Co. Ltd, Qingdao, China
| | - Guo-Hu Di
- School of Basic Medicine, Qingdao University, 308 Ningxia Road, Qingdao, 266071, China.
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29
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Weiss JB, Phillips CJ, Malin EW, Gorantla VS, Harding JW, Salgar SK. Stem cell, Granulocyte-Colony Stimulating Factor and/or Dihexa to promote limb function recovery in a rat sciatic nerve damage-repair model: Experimental animal studies. Ann Med Surg (Lond) 2021; 71:102917. [PMID: 34703584 PMCID: PMC8524106 DOI: 10.1016/j.amsu.2021.102917] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2021] [Accepted: 10/05/2021] [Indexed: 11/04/2022] Open
Abstract
Background Optimizing nerve regeneration and re-innervation of target muscle/s is the key for improved functional recovery following peripheral nerve damage. We investigated whether administration of mesenchymal stem cell (MSC), Granulocyte-Colony Stimulating Factor (G-CSF) and/or Dihexa can improve recovery of limb function following peripheral nerve damage in rat sciatic nerve transection-repair model. Materials and methods There were 10 experimental groups (n = 6–8 rats/group). Bone marrow derived syngeneic MSCs (2 × 106; passage≤6), G-CSF (200–400 μg/kg b.wt.), Dihexa (2–4 mg/kg b.wt.) and/or Vehicle were administered to male Lewis rats locally via hydrogel at the site of nerve repair, systemically (i.v./i.p), and/or to gastrocnemius muscle. The limb sensory and motor functions were assessed at 1–2 week intervals post nerve repair until the study endpoint (16 weeks). Results The sensory function in all nerve boundaries (peroneal, tibial, sural) returned to nearly normal by 8 weeks (Grade 2.7 on a scale of Grade 0–3 [0 = No function; 3 = Normal function]) in all groups combined. The peroneal nerve function recovered quickly with return of function at one week (∼2.0) while sural nerve function recovered rather slowly at four weeks (∼1.0). Motor function at 8–16 weeks post-nerve repair as determined by walking foot print grades significantly (P < 0.05) improved with MSC + G-CSF or MSC + Dihexa administrations into gastrocnemius muscle and mitigated foot flexion contractures. Conclusions These findings demonstrate MSC, G-CSF and Dihexa are promising candidates for adjunct therapies to promote limb functional recovery after surgical nerve repair, and have implications in peripheral nerve injury and limb transplantation. IACUC No.215064.
G-CSF in combination with MSCs improved limb function recovery in sciatic nerve transection- repair model. Dihexa in combination with MSC improved limb function recovery in sciatic nerve transection- repair model. Foot flexion contractures were reduced with G-CSF & MSC or Dihexa & MSC administration into target muscle gastrocnemius. MSC, G-CSF or Dihexa combination therapy is attractive, feasible & promising in peripheral nerve injury repair and have implications in limb transplantation. The findings warrant further investigation to understand the cellular/molecular mechanisms.
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Affiliation(s)
- Jessica B Weiss
- Department of Surgery, Madigan Army Medical Center, Tacoma, Fort Lewis, Washington, USA
| | - Cody J Phillips
- Department of Surgery, Madigan Army Medical Center, Tacoma, Fort Lewis, Washington, USA
| | - Edward W Malin
- Department of Surgery, Madigan Army Medical Center, Tacoma, Fort Lewis, Washington, USA
| | - Vijay S Gorantla
- Department of Surgery, Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA
| | - Joseph W Harding
- Department of Integrative Physiology & Neuroscience, Washington State University, Pullman, WA, USA
| | - Shashikumar K Salgar
- Department of Clinical Investigation, Madigan Army Medical Center, Tacoma, Fort Lewis, Washington, USA
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30
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Zhu Q, Hao H, Xu H, Fichman Y, Cui Y, Yang C, Wang M, Mittler R, Hill MA, Cowan PJ, Zhang G, He X, Zhou S, Liu Z. Combination of Antioxidant Enzyme Overexpression and N-Acetylcysteine Treatment Enhances the Survival of Bone Marrow Mesenchymal Stromal Cells in Ischemic Limb in Mice With Type 2 Diabetes. J Am Heart Assoc 2021; 10:e023491. [PMID: 34569277 PMCID: PMC8649154 DOI: 10.1161/jaha.121.023491] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
Background Therapy with mesenchymal stem cells remains a promising but challenging approach to critical limb ischemia in diabetes because of the dismal cell survival. Methods and Results Critical limb ischemia in type 2 diabetes mouse model was used to explore the impact of diabetic limb ischemia on the survival of bone marrow mesenchymal stromal cells (bMSCs). Inhibition of intracellular reactive oxygen species was achieved with concomitant overexpression of superoxide dismutase (SOD)‐1 and glutathione peroxidase‐1 in the transplanted bMSCs, and extracellular reactive oxygen species was attenuated using SOD‐3 overexpression and N‐acetylcysteine treatment. In vivo optical fluorescence imaging and laser Doppler perfusion imaging were used to track cell retention and determine blood flow in diabetic ischemic limb, respectively. Survival of the transplanted bMSCs was significantly decreased in diabetic ischemic limb compared with the control. In vitro study indicated that advanced glycation end products, not high glucose, significantly decreased the proliferation of bMSCs and increased their apoptosis associated with increased reactive oxygen species production and selective reduction of SOD‐1 and SOD‐3. In vivo study demonstrated that concomitant overexpression of SOD‐1, SOD‐3, and glutathione peroxidase‐1, or host treatment with N‐acetylcysteine, significantly enhanced in vivo survival of transplanted bMSCs, and improved critical limb ischemia in diabetic mice. Combination of triple antioxidant enzyme overexpression in bMSCs with host N‐acetylcysteine treatment further improved bMSC survival with enhanced circulatory and functional recovery from diabetic critical limb ischemia. Conclusions Simultaneous suppression of reactive oxygen species from transplanted bMSCs and host tissue could additively enhance bMSC survival in diabetic ischemic limb with increased therapeutic efficacy in diabetes.
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Affiliation(s)
- Qiang Zhu
- Center for Precision Medicine and Division of Cardiovascular Medicine Department of Medicine University of Missouri School of Medicine Columbia MO.,Department of Cardiology Second Xiangya Hospital Central South University Changsha City Hunan Province China
| | - Hong Hao
- Center for Precision Medicine and Division of Cardiovascular Medicine Department of Medicine University of Missouri School of Medicine Columbia MO
| | - Huifang Xu
- Center for Precision Medicine and Division of Cardiovascular Medicine Department of Medicine University of Missouri School of Medicine Columbia MO
| | - Yosef Fichman
- College of Agriculture, Food and Natural Resources University of Missouri Columbia MO.,Dalton Cardiovascular Research Center University of Missouri Columbia MO
| | - Yuqi Cui
- Center for Precision Medicine and Division of Cardiovascular Medicine Department of Medicine University of Missouri School of Medicine Columbia MO
| | - Chunlin Yang
- Center for Precision Medicine and Division of Cardiovascular Medicine Department of Medicine University of Missouri School of Medicine Columbia MO
| | - Meifang Wang
- Center for Precision Medicine and Division of Cardiovascular Medicine Department of Medicine University of Missouri School of Medicine Columbia MO
| | - Ron Mittler
- College of Agriculture, Food and Natural Resources University of Missouri Columbia MO.,Dalton Cardiovascular Research Center University of Missouri Columbia MO
| | - Michael A Hill
- Dalton Cardiovascular Research Center University of Missouri Columbia MO.,Department of Surgery University of Missouri School of MedicineChristopher S. Bond Life Sciences CenterUniversity of Missouri Columbia MO
| | - Peter J Cowan
- Department of Medicine University of Melbourne Australia.,Immunology Research Centre St. Vincent's Hospital Melbourne Australia
| | - Guangsen Zhang
- Institute of Molecular Hematopathy Second Xiangya Hospital Central South University Changsha City Hunan Province China
| | - Xiaoming He
- Fischell Department of Bioengineering University of Maryland College Park MD
| | - Shenghua Zhou
- Department of Cardiology Second Xiangya Hospital Central South University Changsha City Hunan Province China
| | - Zhenguo Liu
- Center for Precision Medicine and Division of Cardiovascular Medicine Department of Medicine University of Missouri School of Medicine Columbia MO
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31
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Matheakakis A, Batsali A, Papadaki HA, Pontikoglou CG. Therapeutic Implications of Mesenchymal Stromal Cells and Their Extracellular Vesicles in Autoimmune Diseases: From Biology to Clinical Applications. Int J Mol Sci 2021; 22:10132. [PMID: 34576296 PMCID: PMC8468750 DOI: 10.3390/ijms221810132] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2021] [Revised: 09/14/2021] [Accepted: 09/15/2021] [Indexed: 12/11/2022] Open
Abstract
Mesenchymal stromal cells (MSCs) are perivascular multipotent stem cells originally identified in the bone marrow (BM) stroma and subsequently in virtually all vascularized tissues. Because of their ability to differentiate into various mesodermal lineages, their trophic properties, homing capacity, and immunomodulatory functions, MSCs have emerged as attractive candidates in tissue repair and treatment of autoimmune disorders. Accumulating evidence suggests that the beneficial effects of MSCs may be primarily mediated via a number of paracrine-acting soluble factors and extracellular vesicles (EVs). EVs are membrane-coated vesicles that are increasingly being acknowledged as playing a key role in intercellular communication via their capacity to carry and deliver their cargo, consisting of proteins, nucleic acids, and lipids to recipient cells. MSC-EVs recapitulate the functions of the cells they originate, including immunoregulatory effects but do not seem to be associated with the limitations and concerns of cell-based therapies, thereby emerging as an appealing alternative therapeutic option in immune-mediated disorders. In the present review, the biology of MSCs will be outlined and an overview of their immunomodulatory functions will be provided. In addition, current knowledge on the features of MSC-EVs and their immunoregulatory potential will be summarized. Finally, therapeutic applications of MSCs and MSC-EVs in autoimmune disorders will be discussed.
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Affiliation(s)
- Angelos Matheakakis
- Department of Hematology, School of Medicine, University of Crete, 71500 Heraklion, Greece; (A.M.); (H.A.P.)
- Haemopoiesis Research Laboratory, School of Medicine, University of Crete, 71500 Heraklion, Greece;
| | - Aristea Batsali
- Haemopoiesis Research Laboratory, School of Medicine, University of Crete, 71500 Heraklion, Greece;
| | - Helen A. Papadaki
- Department of Hematology, School of Medicine, University of Crete, 71500 Heraklion, Greece; (A.M.); (H.A.P.)
- Haemopoiesis Research Laboratory, School of Medicine, University of Crete, 71500 Heraklion, Greece;
| | - Charalampos G. Pontikoglou
- Department of Hematology, School of Medicine, University of Crete, 71500 Heraklion, Greece; (A.M.); (H.A.P.)
- Haemopoiesis Research Laboratory, School of Medicine, University of Crete, 71500 Heraklion, Greece;
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Ebrahim N, Dessouky AA, Mostafa O, Hassouna A, Yousef MM, Seleem Y, El Gebaly EAEAM, Allam MM, Farid AS, Saffaf BA, Sabry D, Nawar A, Shoulah AA, Khalil AH, Abdalla SF, El-Sherbiny M, Elsherbiny NM, Salim RF. Adipose mesenchymal stem cells combined with platelet-rich plasma accelerate diabetic wound healing by modulating the Notch pathway. Stem Cell Res Ther 2021; 12:392. [PMID: 34256844 PMCID: PMC8276220 DOI: 10.1186/s13287-021-02454-y] [Citation(s) in RCA: 60] [Impact Index Per Article: 15.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2021] [Accepted: 06/12/2021] [Indexed: 02/08/2023] Open
Abstract
Background Diabetic foot ulceration is a serious chronic complication of diabetes mellitus characterized by high disability, mortality, and morbidity. Platelet-rich plasma (PRP) has been widely used for diabetic wound healing due to its high content of growth factors. However, its application is limited due to the rapid degradation of growth factors. The present study aimed to evaluate the efficacy of combined adipose-derived mesenchymal stem cells (ADSCs) and PRP therapy in promoting diabetic wound healing in relation to the Notch signaling pathway. Methods Albino rats were allocated into 6 groups [control (unwounded), sham (wounded but non-diabetic), diabetic, PRP-treated, ADSC-treated, and PRP+ADSCs-treated groups]. The effect of individual and combined therapy was evaluated by assessing wound closure rate, epidermal thickness, dermal collagen, and angiogenesis. Moreover, gene and protein expression of key elements of the Notch signaling pathway (Notch1, Delta-like canonical Notch ligand 4 (DLL4), Hairy Enhancer of Split-1 (Hes1), Hey1, Jagged-1), gene expression of angiogenic marker (vascular endothelial growth factor and stromal cell-derived factor 1) and epidermal stem cells (EPSCs) related gene (ß1 Integrin) were assessed. Results Our data showed better wound healing of PRP+ADSCs compared to their individual use after 7 and 14 days as the combined therapy caused reepithelialization and granulation tissue formation with a marked increase in area percentage of collagen, epidermal thickness, and angiogenesis. Moreover, Notch signaling was significantly downregulated, and EPSC proliferation and recruitment were enhanced compared to other treated groups and diabetic groups. Conclusions These data demonstrated that PRP and ADSCs combined therapy significantly accelerated healing of diabetic wounds induced experimentally in rats via modulating the Notch pathway, promoting angiogenesis and EPSC proliferation.
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Affiliation(s)
- Nesrine Ebrahim
- Department of Histology and Cell Biology Faculty of Medicine, Benha University, Benha, Egypt.,Stem Cell Unit, Faculty of Medicine, Benha University, Benha, Egypt
| | - Arigue A Dessouky
- Department of Histology and Cell Biology, Faculty of Medicine, Zagazig University, Zagazig, Egypt
| | - Ola Mostafa
- Department of Histology and Cell Biology Faculty of Medicine, Benha University, Benha, Egypt
| | - Amira Hassouna
- School of Interprofessional Health Studies, Faculty of Health and Environmental Sciences, AUT University, Auckland, New Zealand
| | - Mohamed M Yousef
- Department of Histology and Cell Biology Faculty of Medicine, Benha University, Benha, Egypt
| | - Yasmin Seleem
- Department of Clinical Pharmacology, Faculty of Medicine, Benha University, Benha, Egypt
| | | | - Mona M Allam
- Department of Medical Physiology, Faculty of Medicine, Benha University, Benha, Egypt
| | - Ayman Samir Farid
- Department of Clinical Pathology, Faculty of Veterinary Medicine, Benha University, Moshtohor, Toukh, Qalyubia, 13736, Egypt
| | - Bayan A Saffaf
- Department of Pharmacology, Faculty of Pharmacy, Future University, New Cairo, Egypt
| | - Dina Sabry
- Department of Medical Biochemistry and Molecular Biology, Faculty of Medicine, Cairo University, Cairo, Egypt.,Department of Medical Biochemistry and Molecular Biology, Faculty of Medicine, Badr University, Cairo, 11562, Egypt
| | - Ahmed Nawar
- Department of General Surgery, Faculty of Medicine, Benha University, Benha, Egypt
| | - Ahmed A Shoulah
- Department of General Surgery, Faculty of Medicine, Benha University, Benha, Egypt
| | - Ahmed H Khalil
- Department of Surgery, & Radiology Faculty of Veterinary Medicine, Benha University, Benha, Egypt
| | - Sami F Abdalla
- Clinical Department, College of Medicine, AlMaarefa University, Riyadh, Saudi Arabia
| | - Mohamed El-Sherbiny
- Department of Basic Medical Sciences, College of Medicine, AlMaarefa University, Riyadh, Saudi Arabia.,Department of Anatomy, Faculty of Medicine, Mansoura University, Mansoura, Egypt
| | - Nehal M Elsherbiny
- Department of Biochemistry, Faculty of Pharmacy, Mansoura University, Mansoura, 35516, Egypt. .,Department of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Tabuk, Tabuk, Saudi Arabia.
| | - Rabab F Salim
- Department of Medical Biochemistry and Molecular Biology, Faculty of Medicine, Benha University, Benha, Egypt.
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33
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LIU L, YANG F. Application of Modified Mesenchymal Stem Cells Transplantation in the Treatment of Liver Injury. Physiol Res 2021. [DOI: 10.33549/physiolres.934623] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022] Open
Abstract
Acute and chronic hepatitis, cirrhosis, and other liver diseases pose a serious threat to human health; however, liver transplantation is the only reliable treatment for the terminal stage of liver diseases. Previous researchers have shown that mesenchymal stem cells (MSCs) are characterized by differentiation and paracrine effects, as well as anti-oxidative stress and immune regulation functions. When MSCs are transplanted into animals, they migrate to the injured liver tissue along with the circulation, to protect the liver and alleviate the injury through the paracrine, immune regulation and other characteristics, making mesenchymal stem cell transplantation a promising alternative therapy for liver diseases. Although the efficacy of MSCs transplantation has been confirmed in various animal models of liver injury, many researchers have also proposed various pretreatment methods to improve the efficacy of mesenchymal stem cell transplantation, but there is still lack a set of scientific methods system aimed at improving the efficacy of transplantation therapy in scientific research and clinical practice. In this review, we summarize the possible mechanisms of MSCs therapy and compare the existing methods of MSCs modification corresponding to the treatment mechanism, hoping to provide as a reference to help future researchers explore a safe and simple transplantation strategy.
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Affiliation(s)
- L LIU
- School of Basic Medicine, Yangtze University Health Science Center, Jingzhou, China
| | - F YANG
- School of Basic Medicine, Yangtze University Health Science Center, Jingzhou, China
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34
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Ammar LA, Nahlawi MI, Shayya NW, Ghadieh HE, Azar NS, Harb F, Eid AA. Immunomodulatory Approaches in Diabetes-Induced Cardiorenal Syndromes. Front Cardiovasc Med 2021; 7:630917. [PMID: 33585587 PMCID: PMC7876252 DOI: 10.3389/fcvm.2020.630917] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2020] [Accepted: 12/31/2020] [Indexed: 12/16/2022] Open
Abstract
Immunomodulatory approaches are defined as all interventions that modulate and curb the immune response of the host rather than targeting the disease itself with the aim of disease prevention or treatment. A better understanding of the immune system continues to offer innovative drug targets and methods for immunomodulatory interventions. Cardiorenal syndrome is a clinical condition that defines disorders of the heart and kidneys, both of which communicate with one another through multiple pathways in an interdependent relationship. Cardiorenal syndrome denotes the confluence of heart-kidney relationships across numerous interfaces. As such, a dysfunctional heart or kidney has the capacity to initiate disease in the other organ via common hemodynamic, neurohormonal, immunological, and/or biochemical feedback pathways. Understanding how immunomodulatory approaches are implemented in diabetes-induced cardiovascular and renal diseases is important for a promising regenerative medicine, which is the process of replacing cells, tissues or organs to establish normal function. In this article, after a brief introduction on the immunomodulatory approaches in diseases, we will be reviewing the epidemiology and classifications of cardiorenal syndrome. We will be emphasizing on the hemodynamic factors and non-hemodynamic factors linking the heart and the kidneys. In addition, we will be elaborating on the immunomodulatory pathways involved in diabetes-induced cardiorenal syndrome namely, RAS, JAK/STAT, and oxidative stress. Moreover, we will be addressing possible therapeutic approaches that target the former pathways in an attempt to modulate the immune system.
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Affiliation(s)
- Lama A Ammar
- Department of Anatomy, Cell Biology and Physiological Sciences, Faculty of Medicine and Medical Center, American University of Beirut, Beirut, Lebanon.,American University of Beirut Diabetes, American University of Beirut, Beirut, Lebanon
| | - Mohamad I Nahlawi
- Department of Anatomy, Cell Biology and Physiological Sciences, Faculty of Medicine and Medical Center, American University of Beirut, Beirut, Lebanon.,American University of Beirut Diabetes, American University of Beirut, Beirut, Lebanon
| | - Nizar W Shayya
- Department of Anatomy, Cell Biology and Physiological Sciences, Faculty of Medicine and Medical Center, American University of Beirut, Beirut, Lebanon.,American University of Beirut Diabetes, American University of Beirut, Beirut, Lebanon
| | - Hilda E Ghadieh
- Department of Anatomy, Cell Biology and Physiological Sciences, Faculty of Medicine and Medical Center, American University of Beirut, Beirut, Lebanon.,American University of Beirut Diabetes, American University of Beirut, Beirut, Lebanon
| | - Nadim S Azar
- Department of Anatomy, Cell Biology and Physiological Sciences, Faculty of Medicine and Medical Center, American University of Beirut, Beirut, Lebanon.,American University of Beirut Diabetes, American University of Beirut, Beirut, Lebanon
| | - Frédéric Harb
- Department of Life and Earth Sciences, Faculty of Sciences, Lebanese University, Fanar, Lebanon
| | - Assaad A Eid
- Department of Anatomy, Cell Biology and Physiological Sciences, Faculty of Medicine and Medical Center, American University of Beirut, Beirut, Lebanon.,American University of Beirut Diabetes, American University of Beirut, Beirut, Lebanon
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Mesenchymal Stem Cells Attenuate Acute Liver Failure by Promoting Expansion of Regulatory T Cells in an Indoleamine 2,3-Dioxygenase-Dependent Manner. SERBIAN JOURNAL OF EXPERIMENTAL AND CLINICAL RESEARCH 2020. [DOI: 10.2478/sjecr-2018-0043] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022] Open
Abstract
Abstract
The influence of mesenchymal stem cells (MSCs) on the phenotype and function of CD4+CD49b+FoxP3- regulatory cells has not been elucidated. We used Concanavalin A (ConA) - and α-galactosylceramide (α-GalCer)-induced acute liver injury to estimate the effects of MSCs on liver-infiltrating CD4+CD49b+FoxP3-regulatory cells. MSCs significantly reduced ConA- and α-GalCer-mediated liver injury in C57BL/6 mice, as demonstrated by biochemical tests, reduced influx of inflammatory CD4+ T cells, and increased presence of CD4+CD49b+FoxP3- regulatory cells in the injured livers. The number of CD4+CD49b+FoxP3-regulatory cells was also significantly increased in α-GalCer-treated mice that received MSC-derived conditioned medium (MSC-CM). The presence of 1-methyltryptophan, a specific inhibitor of indoleamine 2,3-dioxygenase (IDO), in MSC-CM completely abrogated the hepatoprotective eff ect of MSCs and significantly decreased the total number of liver-infiltrated CD4+CD49b+FoxP3- regulatory cells, indicating the crucial importance of MSC-derived IDO for the expansion of CD4+CD49b+FoxP3- regulatory cells and the consequent MSC-dependent attenuation of acute liver injury.
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Goenka V, Borkar T, Desai A, Das RK. Therapeutic potential of mesenchymal stem cells in treating both types of diabetes mellitus and associated diseases. J Diabetes Metab Disord 2020; 19:1979-1993. [PMID: 33520872 PMCID: PMC7843693 DOI: 10.1007/s40200-020-00647-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/08/2020] [Accepted: 09/24/2020] [Indexed: 10/23/2022]
Abstract
Diabetes mellitus is a common lifestyle disease which can be classified into type 1 diabetes mellitus and type 2 diabetes mellitus. While both result in hyperglycemia due to lack of insulin action and further associated chronic ailments, there is a marked distinction in the cause for each type due to which both require a different prophylaxis. As observed, type 1 diabetes is caused due to the autoimmune action of the body resulting in the destruction of pancreatic islet cells. On the other hand, type 2 diabetes is caused either due to insulin resistance of target cells or lack of insulin production as per physiological requirements. Attempts to cure the disease have been made by bringing drastic changes in the patients' lifestyle; parenteral administration of insulin; prescription of drugs such as biguanides, meglitinides, and amylin; pancreatic transplantation; and immunotherapy. While these attempts cause a certain degree of relief to the patient, none of these can cure diabetes mellitus. However, a new treatment strategy led by the discovery of mesenchymal stem cells and their unique immunomodulatory and multipotent properties has inspired therapies to treat diabetes by essentially reversing the conditions causing the disease. The current review aims to enumerate the role of various mesenchymal stem cells and the different approaches to treat both types of diabetes and its associated diseases as well.
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Affiliation(s)
- Vidul Goenka
- School of Biosciences and Technology, Vellore Institute of Technology, Vellore, Tamil Nadu India
| | - Tanhai Borkar
- School of Biosciences and Technology, Vellore Institute of Technology, Vellore, Tamil Nadu India
| | - Aska Desai
- School of Biosciences and Technology, Vellore Institute of Technology, Vellore, Tamil Nadu India
| | - Raunak Kumar Das
- Centre for Biomaterials, Cellular and Molecular Theranostics, Vellore Institute of Technology, Vellore, Tamil Nadu India
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Wu KC, Weng HK, Hsu YS, Huang PJ, Wang YK. Aqueous extract of Arctium lappa L. root (burdock) enhances chondrogenesis in human bone marrow-derived mesenchymal stem cells. BMC Complement Med Ther 2020; 20:364. [PMID: 33228629 PMCID: PMC7686739 DOI: 10.1186/s12906-020-03158-1] [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: 04/06/2020] [Accepted: 11/13/2020] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND Arctium lappa L. root (burdock root) has long been recommended for the treatment of different diseases in traditional Chinese medicine. Burdock root possesses anti-oxidative, anti-inflammatory, anti-cancer, and anti-microbial activities. The aim of the study was to elucidate whether aqueous extract of burdock root regulates mesenchymal stem cell proliferation and differentiation. METHODS Human bone marrow-derived mesenchymal stem cells in 2D high density culture and in 3D micromass pellets were treated with chondrogenic induction medium and chondral basal medium in the absence or presence of aqueous extract of burdock root. The chondrogenic differentiation was accessed by staining glucosaminoglycans, immunostaining SOX9 and type II collagen and immuonblotting of SOX9, aggrecan and type II collagen. RESULTS Treatment of aqueous extract of burdock root increased the cell proliferation of hMSCs. It did not have significant effect on osteogenic and adipogenic differentiation, but significantly enhanced chondrogenic induction medium-induced chondrogenesis. The increment was dose dependent, as examined by staining glucosaminoglycans, SOX9, and type II collagen and immunobloting of SOX9, aggrecan and type II collagen in 2D and 3D cultures. In the presence of supplemental materials, burdock root aqueous extract showed equivalent chondrogenic induction capability to that of TGF-β. CONCLUSIONS The results demonstrate that aqueous extract of Arctium lappa L. root promotes chondrogenic medium-induced chondrogenic differentiation. The aqueous extract of burdock root can even be used alone to stimulate chondrogenic differentiation. The study suggests that the aqueous extract of burdock root can be used as an alternative strategy for treatment purposes.
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Affiliation(s)
- King-Chuen Wu
- Department of Nursing, Chang Gung University of Science and Technology, Chia-Yi County, Taiwan.,Department of Anesthesiology, Chang Gung Memorial Hospital, Chiayi County, Taiwan
| | - Hung-Kai Weng
- Department of Orthopaedics, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan City, Taiwan.,Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan City, Taiwan
| | - Yun-Shang Hsu
- Department of Cell Biology and Anatomy, College of Medicine, National Cheng Kung University, Tainan City, Taiwan
| | - Pin-Jia Huang
- Department of Cell Biology and Anatomy, College of Medicine, National Cheng Kung University, Tainan City, Taiwan
| | - Yang-Kao Wang
- Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan City, Taiwan. .,Department of Cell Biology and Anatomy, College of Medicine, National Cheng Kung University, Tainan City, Taiwan.
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Liu D, Zheng W, Pan S, Liu Z. Concise review: current trends on applications of stem cells in diabetic nephropathy. Cell Death Dis 2020; 11:1000. [PMID: 33221823 PMCID: PMC7680458 DOI: 10.1038/s41419-020-03206-1] [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: 07/01/2020] [Revised: 10/27/2020] [Accepted: 10/27/2020] [Indexed: 12/15/2022]
Abstract
Diabetic nephropathy, with high prevalence, is the main cause of renal failure in diabetic patients. The strategies for treating DN are limited with not only high cost but an unsatisfied effect. Therefore, the effective treatment of DN needs to be explored urgently. In recent years, due to their self-renewal ability and multi-directional differentiation potential, stem cells have exerted therapeutic effects in many diseases, such as graft-versus-host disease, autoimmune diseases, pancreatic diseases, and even acute kidney injury. With the development of stem cell technology, stem cell-based regenerative medicine has been tried to be applied to the treatment of DN. Related stem cells include embryonic stem cells, induced pluripotent stem cells, mesenchymal cells, and endothelial progenitor cells. Undoubtedly, stem cell transplantation has achieved certain results in the treatment of DN animal models. However, stem cell therapy still remains certain thorny issues during treatment. For instance, poor engraftment and limited differentiation of stem cells caused by the diabetic microenvironment, differentiation into unwanted cell lineages, and malignant transformation or genetic aberrations of stem cells. At present, various researches on the therapeutic effects of stem cells in DN with different opinions are reported and the specific mechanism of stem cells is still unclear. We review here the potential mechanism of stem cells as new therapeutic agents in the treatment of DN. Also, we review recent findings and updated information about not only the utilization of stem cells on DN in both preclinical and clinical trials but limitations and future expectations of stem cell-based therapy for DN.
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Affiliation(s)
- Dongwei Liu
- Department of Nephrology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, P.R. China.,Research Institute of Nephrology, Zhengzhou University, Zhengzhou, 450052, P.R. China.,Key Laboratory of Precision Diagnosis and Treatment for Chronic Kidney Disease in Henan Province, Zhengzhou, 450052, P.R. China.,Core Unit of National Clinical Medical Research Center of Kidney Disease, Zhengzhou, 450052, P.R. China
| | - Wen Zheng
- Department of Nephrology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, P.R. China.,Research Institute of Nephrology, Zhengzhou University, Zhengzhou, 450052, P.R. China.,Key Laboratory of Precision Diagnosis and Treatment for Chronic Kidney Disease in Henan Province, Zhengzhou, 450052, P.R. China.,Core Unit of National Clinical Medical Research Center of Kidney Disease, Zhengzhou, 450052, P.R. China
| | - Shaokang Pan
- Department of Nephrology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, P.R. China.,Research Institute of Nephrology, Zhengzhou University, Zhengzhou, 450052, P.R. China.,Key Laboratory of Precision Diagnosis and Treatment for Chronic Kidney Disease in Henan Province, Zhengzhou, 450052, P.R. China.,Core Unit of National Clinical Medical Research Center of Kidney Disease, Zhengzhou, 450052, P.R. China
| | - Zhangsuo Liu
- Department of Nephrology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, P.R. China. .,Research Institute of Nephrology, Zhengzhou University, Zhengzhou, 450052, P.R. China. .,Key Laboratory of Precision Diagnosis and Treatment for Chronic Kidney Disease in Henan Province, Zhengzhou, 450052, P.R. China. .,Core Unit of National Clinical Medical Research Center of Kidney Disease, Zhengzhou, 450052, P.R. China.
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Abstract
Over the last decade, there has been a considerable progress in the development of cell therapy products for the treatment of liver diseases. The quest to generate well-defined homogenous cell populations with defined mechanism(s) of action has enabled the progression from use of autologous bone marrow stem cells comprising of heterogeneous cell populations to allogeneic cell types such as monocyte-derived macrophages, regulatory T cells, mesenchymal stromal cells, macrophages, etc. There is growing evidence regarding the multiple molecular mechanisms pivotal to various therapeutic effects and hence, careful selection of cell therapy product for the desired putative effects is crucial. In this review, we have presented an overview of the cell therapies that have been developed thus far, with preclinical and clinical evidence for their use in liver disease. Limitations associated with these therapies have also been discussed. Despite the advances made, there remain multiple challenges to overcome before cell therapies can be considered as viable treatment options, and these include larger scale clinical trials, scalable production of cells according to good manufacturing practice standards, pathways for delivery of cell therapy within hospital environments, and costs associated with the production.
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Affiliation(s)
- Sheeba Khan
- National Institute for Health Research (NIHR) Birmingham Biomedical Research Centre, University Hospitals Birmingham NHS Foundation Trust, University of Birmingham, Birmingham, United Kingdom.,Centre for Liver Research, Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, United Kingdom.,Liver Unit, University Hospitals Birmingham NHS Foundation Trust, Birmingham, United Kingdom
| | - Reenam S Khan
- National Institute for Health Research (NIHR) Birmingham Biomedical Research Centre, University Hospitals Birmingham NHS Foundation Trust, University of Birmingham, Birmingham, United Kingdom.,Centre for Liver Research, Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, United Kingdom.,Liver Unit, University Hospitals Birmingham NHS Foundation Trust, Birmingham, United Kingdom
| | - Philip N Newsome
- National Institute for Health Research (NIHR) Birmingham Biomedical Research Centre, University Hospitals Birmingham NHS Foundation Trust, University of Birmingham, Birmingham, United Kingdom.,Centre for Liver Research, Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, United Kingdom.,Liver Unit, University Hospitals Birmingham NHS Foundation Trust, Birmingham, United Kingdom
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40
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Sharma S, Bhonde R. Genetic and epigenetic stability of stem cells: Epigenetic modifiers modulate the fate of mesenchymal stem cells. Genomics 2020; 112:3615-3623. [DOI: 10.1016/j.ygeno.2020.04.022] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2019] [Revised: 04/08/2020] [Accepted: 04/24/2020] [Indexed: 12/11/2022]
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Restoration of estrous cycles by co-transplantation of mouse ovarian tissue with MSCs. Cell Tissue Res 2020; 381:509-525. [PMID: 32424509 DOI: 10.1007/s00441-020-03204-x] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/04/2019] [Accepted: 03/12/2020] [Indexed: 12/13/2022]
Abstract
This study investigates the effect of bone marrow (BM-MSCs) and visceral peritoneum (VP-MSCs)-derived mesenchymal stem cells on the transplanted ovary. VP-MSCs and BM-MSCs were obtained from green fluorescent protein-expressing mice (GFP+). Six- to eight-week-old female NMRI mice were divided into four experimental groups, autograft ovarian tissue fragments (AO), autograft ovarian tissue fragments encapsulated in fibrin-collagen hydrogel (AO-H), autograft ovarian tissue fragments encapsulated in fibrin-collagen hydrogel containing BM-MSCs (AO-HB) and autograft ovarian tissue fragments encapsulated in fibrin-collagen hydrogel containing VP-MSCs (AO-HP). Intact ovary (IO) was the control group. The estrous cycles resumption time was monitored and at the third estrous cycle, the blood samples and grafted ovaries were evaluated using hormonal, histological and gene expression analysis. Onset of estrous cycles, especially at the second cycle, was earlier in AO-HB and AO-HP groups than in the AO-H group (P < 0.05). Moreover, E2 and FSH levels in AO-HB and AO-HP groups were returned to those of the intact group. However, folliculogenesis was still retarded as compared with the IO group. The gene expression of theca (Lhcgr, Cyp17a1, Gli2, Gli3 and Ptch1), granulosa (Amh and Fshr), oocyte (Zp3 and Gdf9), germ cells (Stella and Prdm1), angiogenesis (VEGF and bFGF) and apoptosis (Bax/Bcl2 and Caspase3) markers was similar in both AO-HB and AO-HP groups. Expression of Amh, Fshr, Gdf9 and VEGF increased only in the AO-HP group whereas expression of Ptch1 increased only in the AO-HB group, as compared with the AO group (P < 0.05). In conclusion, BM-MSCs or VP-MSCs can improve ovarian autotransplantation in mice with no superiority over each other.
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Hashemi SM, Hassan ZM, Hossein-Khannazer N, Pourfathollah AA, Soudi S. Investigating the route of administration and efficacy of adipose tissue-derived mesenchymal stem cells and conditioned medium in type 1 diabetic mice. Inflammopharmacology 2020; 28:585-601. [PMID: 31741175 DOI: 10.1007/s10787-019-00661-x] [Citation(s) in RCA: 28] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/03/2019] [Accepted: 10/29/2019] [Indexed: 12/11/2022]
Abstract
Type 1 diabetes (T1D) is a chronic autoimmune disease destroying the insulin-producing beta cells. Recently, stem cell therapy has been tested to treat T1D. In the present study, we aim to investigate the effects of intraperitoneal and intravenous infusion of multipotent mesenchymal stem/stromal cells (MSCs) and MSC-conditioned medium (MSC-CM) in an experimental model of diabetes, induced by multiple injections of Streptozotocin (STZ). The adipose tissue-derived MSC and MSC-CM were isolated from C57Bl/6 male mice and characterized. Later, MSC and MSC-CM were injected intraperitoneally or intravenously into mice. The blood glucose, urinary glucose, and body weight were measured, and the percentages of CD4+ CD25+ FOXP3+ T cells as well as the levels of IFN-γ, TGF-β, IL-4, IL-17, and IL-10 were evaluated. Our results showed that both intraperitoneal and intravenous infusions of MSC and MSC-CM could decrease the blood glucose, recover pancreatic islets, and increase the levels of insulin-producing cells. Furthermore, the percentage of CD4+ CD25+ FOXP3+ T cells was increased after intraperitoneal injection of MSC or MSC-CM and intravenous injection of MSCs. After intraperitoneal injection of the MSC and MSC-CM, the levels of inflammatory cytokines reduced, while the levels of anti-inflammatory cytokines increased. Together current data showed that although both intraperitoneal and intravenous administration had beneficial effects on T1D animal model, but intraperitoneal injection of AD-MSC and AD-MSC-CM was more effective than systemic administration.
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Affiliation(s)
- Seyed Mahmoud Hashemi
- Department of Immunology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
- Urogenital Stem Cell Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
- Department of Tissue Engineering and Applied Cell Sciences, School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
| | - Zuhair Mohammad Hassan
- Department of Immunology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran.
| | - Nikoo Hossein-Khannazer
- Department of Immunology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Ali Akbar Pourfathollah
- Department of Immunology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran
| | - Sara Soudi
- Department of Immunology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran
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Harrell CR, Markovic BS, Fellabaum C, Arsenijevic N, Djonov V, Volarevic V. The role of Interleukin 1 receptor antagonist in mesenchymal stem cell-based tissue repair and regeneration. Biofactors 2020; 46:263-275. [PMID: 31755595 DOI: 10.1002/biof.1587] [Citation(s) in RCA: 73] [Impact Index Per Article: 14.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/21/2019] [Revised: 09/27/2019] [Accepted: 10/19/2019] [Indexed: 12/13/2022]
Abstract
Interleukin (IL)-1 receptor antagonist (IL-1Ra), a naturally occurring antagonist of IL-1α/IL-1β signaling pathways, has been attributed to the immunosuppressive effects of mesenchymal stem cells (MSCs). MSCs, in IL-1Ra-dependent manner, suppressed production of IL-1β in dermal macrophages, induced their polarization in anti-inflammatory M2 phenotype, attenuated antigen-presenting properties of dendritic cells (DCs), and promoted expansion of immunosuppressive T regulatory cells in the skin, which resulted in enhanced repair of the nonhealing wounds. Reduced activation of inflammasome and suppressed production of IL-1β in macrophages were mainly responsible for beneficial effects of MSC-derived IL-1Ra in alleviation of acute lung injury, dry eye syndrome, and corneal injury. Through the production of IL-1Ra, MSCs reduced migration of DCs to the draining lymph nodes and attenuated generation of inflammatory Th1 and Th17 cells that resulted in alleviation of fulminant hepatitis and rheumatoid arthritis. MSCs, in IL-1Ra-dependent manner, reduced liver fibrosis by suppressing production of Type I collagen in hepatic stellate cells. IL-1Ra was, at least partially, responsible for enhanced proliferation of hepatocytes and chondrocytes in MSC-treated animals with partial hepatectomy and osteoarthritis. Despite of these beneficial effects, IL-1Ra-dependent inhibition of IL-1α/IL-1β-signaling significantly increased risk of infections. Therefore, future experimental and clinical studies should delineate potential side effects of MSC-derived IL-1Ra before IL-1Ra-overexpressing MSCs could be used as a potentially new therapeutic agent for the treatment of acute and chronic inflammatory diseases.
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Affiliation(s)
| | - Bojana Simovic Markovic
- Faculty of Medical Sciences, Department for Microbiology and Immunology, Center for Molecular Medicine and Stem Cell Research, University of Kragujevac, Kragujevac, Serbia
| | | | - Nebojsa Arsenijevic
- Faculty of Medical Sciences, Department for Microbiology and Immunology, Center for Molecular Medicine and Stem Cell Research, University of Kragujevac, Kragujevac, Serbia
| | | | - Vladislav Volarevic
- Faculty of Medical Sciences, Department for Microbiology and Immunology, Center for Molecular Medicine and Stem Cell Research, University of Kragujevac, Kragujevac, Serbia
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44
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Hu C, Wu Z, Li L. Mesenchymal stromal cells promote liver regeneration through regulation of immune cells. Int J Biol Sci 2020; 16:893-903. [PMID: 32071558 PMCID: PMC7019139 DOI: 10.7150/ijbs.39725] [Citation(s) in RCA: 101] [Impact Index Per Article: 20.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/13/2019] [Accepted: 12/26/2019] [Indexed: 02/06/2023] Open
Abstract
The liver is sensitive to pathogen-induced acute or chronic liver injury, and liver transplantation (LT) is the only effective strategy for end-stage liver diseases. However, the clinical application is limited by a shortage of liver organs, immunological rejection and high cost. Mesenchymal stromal cell (MSC)-based therapy has gradually become a hot topic for promoting liver regeneration and repairing liver injury in various liver diseases, since MSCs are reported to migrate toward injured tissues, undergo hepatogenic differentiation, inhibit inflammatory factor release and enhance the proliferation of liver cells in vivo. MSCs exert immunoregulatory effects through cell-cell contact and the secretion of anti-inflammatory factors to inhibit liver inflammation and promote liver regeneration. In addition, MSCs are reported to effectively inhibit the activation of cells of the innate immune system, including macrophages, natural killer (NK) cells, dendritic cells (DCs), monocytes and other immune cells, and inhibit the activation of cells of the adaptive immune system, including T lymphocytes, B lymphocytes and subsets of T cells or B cells. In the current review, we mainly focus on the potential effects and mechanisms of MSCs in inhibiting the activation of immune cells to attenuate liver injury in models or patients with acute liver failure (ALF), nonalcoholic fatty liver disease (NAFLD), and liver fibrosis and in patients or models after LT. We highlight that MSC transplantation may replace general therapies for eliminating acute or chronic liver injury in the near future.
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Affiliation(s)
- Chenxia Hu
- Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, PR China
| | - Zhongwen Wu
- Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, PR China
| | - Lanjuan Li
- Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, PR China
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45
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Klama-Baryła A, Rojczyk E, Kitala D, Łabuś W, Smętek W, Wilemska-Kucharzewska K, Kucharzewski M. Preparation of placental tissue transplants and their application in skin wound healing and chosen skin bullous diseases - Stevens-Johnson syndrome and toxic epidermal necrolysis treatment. Int Wound J 2020; 17:491-507. [PMID: 31943788 DOI: 10.1111/iwj.13305] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2019] [Accepted: 12/17/2019] [Indexed: 12/20/2022] Open
Abstract
Unique properties of amniotic membrane make it a promising source for tissue engineering and a clinically useful alternative for patients suffering from chronic wounds including, for example, ulcers, burns, ocular surface damages and wounds occurring in the course of bullous diseases like stevens-johnson syndrome and toxic epidermal necrolysis. Its use has many advantages over standard wound care, as it contains pluripotent cells, nutrients, anti-fibrotic and anti-inflammatory cytokines, growth factors and extracellular matrix (ECM) proteins. Placental tissues can be prepared as a medical component, an advanced therapy medicinal product or a tissue graft. In addition to basic preparation procedures such as washing, rinsing, cutting, drying and sterilisation, there are many optional steps such as perforation, crosslinking and decellularisation. Finally, transplants should be properly stored-in cryopreserved or dehydrated form. In recent years, many studies including basic science and clinical trials have proven the potential to expand the use of amniotic membrane and amnion-derived cells to the fields of orthopaedics, dentistry, surgery, urology, vascular tissue engineering and even oncology. In this review, we discuss the role of placental tissues in skin wound healing and in the treatment of various diseases, with particular emphasis on bullous diseases. We also describe some patented procedures for placental tissue grafts preparation.
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Affiliation(s)
- Agnieszka Klama-Baryła
- The Burn Centre of Stanisław Sakiel in Siemianowice Śląskie, Siemianowice Śląskie, Poland
| | - Ewa Rojczyk
- Department of Descriptive and Topographic Anatomy, School of Medicine with the Division of Dentistry in Zabrze, Medical University of Silesia, Zabrze, Poland
| | - Diana Kitala
- The Burn Centre of Stanisław Sakiel in Siemianowice Śląskie, Siemianowice Śląskie, Poland
| | - Wojciech Łabuś
- The Burn Centre of Stanisław Sakiel in Siemianowice Śląskie, Siemianowice Śląskie, Poland
| | - Wojciech Smętek
- The Burn Centre of Stanisław Sakiel in Siemianowice Śląskie, Siemianowice Śląskie, Poland
| | | | - Marek Kucharzewski
- Department of Descriptive and Topographic Anatomy, School of Medicine with the Division of Dentistry in Zabrze, Medical University of Silesia, Zabrze, Poland
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46
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Pawitan JA, Margiana R, Aman RA, Jusuf AA, Ibrahim N, Wibowo H. The effect of human umbilical cord-derived mesenchymal stem cell conditioned medium on the peripheral nerve regeneration of injured rats. ELECTRONIC JOURNAL OF GENERAL MEDICINE 2019. [DOI: 10.29333/ejgm/115468] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
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47
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Kanjevac T, Gustafson C, Ivanovska A, Ravanetti F, Cacchioli A, Bosnakovski D. Inflammatory Cytokines and Biodegradable Scaffolds in Dental Mesenchymal Stem Cells Priming. Curr Stem Cell Res Ther 2019; 14:320-326. [PMID: 30608044 DOI: 10.2174/1574888x14666190103170109] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/02/2018] [Revised: 10/15/2018] [Accepted: 11/02/2018] [Indexed: 02/06/2023]
Abstract
Mesenchymal stem cells (MSCs) are multipotent stem cells with wide-ranging clinical applications due to their ability to regenerate tissue from mesenchymal origin and their capability of suppressing immune responses, thus reducing the likelihood of graft versus host disease after transplantation. MSCs can be isolated from a variety of sources including bone marrow, adipose tissue, umbilical cord blood, and immature teeth. Dental stem cells (DSCs) possess progenitor and immunomodulatory abilities as the other MSC types and because they can be easily isolated, are considered as attractive therapeutic agents in regenerative dentistry. Recently, it has been shown that DSCs seeded onto newly developed synthetic biomaterial scaffolds have retained their potential for proliferation and at the same time have enhanced capabilities for differentiation and immunosuppression. The scaffolds are becoming more efficient at MSC priming as researchers learn how short peptide sequences alter the adhesive and proliferative capabilities of the scaffolds by stimulating or inhibiting classical osteogenic pathways. New findings on how to modulate the inflammatory microenvironment, which can prime DSCs for differentiation, combined with the use of next generation scaffolds may significantly improve their therapeutic potential. In this review, we summarize current findings regarding DSCs as a potential regenerative therapy, including stem cell priming with inflammatory cytokines, types of scaffolds currently being explored and the modulation of scaffolds to regulate immune response and promote growth.
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Affiliation(s)
- Tatjana Kanjevac
- Faculty of Medical Sciences, University of Kragujevac, Kragujevac, Serbia
| | - Collin Gustafson
- Lillehei Heart Institute, Department of Pediatrics, University of Minnesota, Minneapolis, United States
| | - Ana Ivanovska
- Department of Veterinary Science, University of Parma, Parma, Italy
| | | | | | - Darko Bosnakovski
- Lillehei Heart Institute, Department of Pediatrics, University of Minnesota, Minneapolis, United States.,Faculty of Medical Sciences, University Goce Delcev, Stip, R. Macedonia
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48
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Treatment with adipose tissue-derived mesenchymal stem cells exerts anti-diabetic effects, improves long-term complications, and attenuates inflammation in type 2 diabetic rats. Stem Cell Res Ther 2019; 10:333. [PMID: 31747961 PMCID: PMC6868748 DOI: 10.1186/s13287-019-1474-8] [Citation(s) in RCA: 96] [Impact Index Per Article: 16.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2019] [Revised: 09/03/2019] [Accepted: 10/30/2019] [Indexed: 02/08/2023] Open
Abstract
Background Long-term diabetes-associated complications are the major causes of morbidity and mortality in individuals with diabetes. These diabetic complications are closely linked to immune system activation along with chronic, non-resolving inflammation, but therapies to directly reverse these complications are still not available. Our previous study demonstrated that mesenchymal stem cells (MSCs) attenuated chronic inflammation in type 2 diabetes mellitus (T2DM), resulting in improved insulin sensitivity and islet function. Therefore, we speculated that MSCs might exert anti-inflammatory effects and promote the reversal of diabetes-induced kidney, liver, lung, heart, and lens diseases in T2DM rats. Methods We induced a long-term T2DM complication rat model by using a combination of a low dose of streptozotocin (STZ) with a high-fat diet (HFD) for 32 weeks. Adipose-derived mesenchymal stem cells (ADSCs) were systemically administered once a week for 24 weeks. Then, we investigated the role of ADSCs in modulating the progress of long-term diabetic complications. Results Multiple infusions of ADSCs attenuated chronic kidney disease (CKD), nonalcoholic steatohepatitis (NASH), lung fibrosis, and cataracts; improved cardiac function; and lowered serum lipid levels in T2DM rats. Moreover, the levels of inflammatory cytokines in the serum of each animal group revealed that ADSC infusions were able to not only inhibit pro-inflammatory cytokines IL-6, IL-1β, and TNF-α expression but also increase anti-inflammatory cytokine IL-10 systematically. Additionally, MSCs reduced the number of iNOS(+) M1 macrophages and restored the number of CD163(+) M2 macrophages. Conclusions Multiple intravenous infusions of ADSCs produced significant protective effects against long-term T2DM complications by alleviating inflammation and promoting tissue repair. The present study suggests ADSCs may be a novel, alternative cell therapy for long-term diabetic complications.
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Hsu MF, Yu SH, Chuang SJ, Kuo TKC, Singal PK, Huang CY, Kao CL, Kuo CH. Can mesenchymal stem cell lysate reverse aging? Aging (Albany NY) 2019; 10:2900-2910. [PMID: 30362957 PMCID: PMC6224235 DOI: 10.18632/aging.101595] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/21/2018] [Accepted: 10/12/2018] [Indexed: 12/16/2022]
Abstract
Recent findings regarding uses of adipose-derived mesenchymal stem cell (MSC)-lysate on weight loss and improved glucose tolerance in mice on a high-fat diet suggest an encouraging possibility of using MSC lysate for an anti-aging intervention in humans. However, weight loss and lipopenia during late life can be as life-threatening as hyperglycemia during early adulthood. For this 3-year lifelong experiment, a total of 92 rats were randomized into the vehicle-injected group (F=22; M=24) and the MSC lysate injected group (F=22, M=24). We examined longevity, spontaneous locomotor activity, and body composition in rats maintained on a normal diet and received an intermittent treatment of human adipose-derived MSC lysate (3 times a week, 11 times a month given every second month), starting at 12 months of age until natural death. In substantiating previous knowledge regarding the effects of long-term MSC lysate treatments on fat loss and insulin resistance, the present findings also highlighted a shortened average lifespan, a longer inactive time, and a greater bone loss with a relative increase of lean mass in MSC lysate rats with respect to controls. Conclusion: Our data suggest that MSC lysate treatments stimulate disparity in tissue development and produce a cachexia-like effect to decrease longevity.
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Affiliation(s)
- Ming-Fen Hsu
- Laboratory of Exercise Biochemistry, University of Taipei, Taipei, Taiwan
| | - Szu-Hsien Yu
- Laboratory of Exercise Biochemistry, University of Taipei, Taipei, Taiwan
| | - Sheng-Ju Chuang
- Laboratory of Exercise Biochemistry, University of Taipei, Taipei, Taiwan.,Université Catholique de Louvain and de Duve Institute, Brussels, Belgium
| | - Tom Kwang-Chun Kuo
- Stem Cell Research Center, National Yang-Ming University, Taipei, Taiwan
| | - Pawan K Singal
- Institute of Cardiovascular Sciences, St Boniface General Hospital Research Centre and Department of Physiology and Pathophysiology, Faculty of Medicine, University of Manitoba, Winnipeg, Canada
| | - Chih-Yang Huang
- Department of Health and Nutrition Biotechnology, Asia University, Taichung, Taiwan.,Graduate Institute of Basic Medical Science, China Medical University, Taichung, Taiwan
| | - Chung-Lan Kao
- Department of Physical Medicine and Rehabilitation, Taipei Veterans General Hospital and National Yang Ming University, Taipei, Taiwan
| | - Chia-Hua Kuo
- Laboratory of Exercise Biochemistry, University of Taipei, Taipei, Taiwan
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50
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Chen L, Forsyth NR, Wu P. Chorionic and amniotic placental membrane-derived stem cells, from gestational diabetic women, have distinct insulin secreting cell differentiation capacities. J Tissue Eng Regen Med 2019; 14:243-256. [PMID: 31701635 DOI: 10.1002/term.2988] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2019] [Revised: 10/04/2019] [Accepted: 10/17/2019] [Indexed: 12/11/2022]
Abstract
Women with gestational diabetes mellitus (GDM), and their offspring, are at high risk of developing type 2 diabetes. Chorionic (CMSCs) and amniotic mesenchymal stem cells (AMSCs) derived from placental membranes provide a source of autologous stem cells for potential diabetes therapy. We established an approach for the CMSC/AMSC-based generation of functional insulin-producing cells (IPCs). CMSCs/AMSCs displayed significantly elevated levels of NANOG and OCT4 versus bone marrow-derived MSCs, indicating a potentially broad differentiation capacity. Exposure of Healthy- and GDM-CMSCs/AMSCs to long-term high-glucose culture resulted in significant declines in viability accompanied by elevation, markedly so in GDM-CMSCs/AMSCs, of senescence/stress markers. Short-term high-glucose culture promoted pancreatic transcription factor expression when coupled to a 16-day step-wise differentiation protocol; activin A, retinoic acid, epidermal growth factor, glucagon-like peptide-1 and other chemical components, generated functional IPCs from both Healthy- and GDM-CMSCs. Healthy-/GDM-AMSCs displayed betacellulin-sensitive insulin expression, which was not secreted upon glucose challenge. The pathophysiological state accompanying GDM may cause irreversible impairment to endogenous AMSCs; however, GDM-CMSCs possess comparable therapeutic potential with Healthy-CMSCs and can be effectively reprogrammed into insulin-secreting cells.
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Affiliation(s)
- Liyun Chen
- School of Pharmacy and Bioengineering, Guy Hilton Research Centre, Keele University Stoke-on-Trent, U.K.,Department of Radiation Oncology, Washington University School of Medicine, St. Louis, Missouri
| | - Nicholas R Forsyth
- School of Pharmacy and Bioengineering, Guy Hilton Research Centre, Keele University Stoke-on-Trent, U.K
| | - Pensee Wu
- School of Pharmacy and Bioengineering, Guy Hilton Research Centre, Keele University Stoke-on-Trent, U.K.,Academic Unit of Obstetrics and Gynaecology, University Hospital of North Midlands Stoke-on-Trent, U.K.,Keele Cardiovascular Research Group, Institute for Applied Clinical Sciences and Centre for Prognosis Research, Institute of Primary Care and Health Sciences, Keele University Stoke-on-Trent, U.K
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