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Lange-Consiglio A, Tagliasacchi F, Cremonesi F, Gusmara C, Pollera C, Scarpa P, Gaspari G, Riccaboni P. Characterization of Urine-Derived Stromal/Stem Cells from Healthy Dogs and Dogs Affected by Chronic Kidney Disease (CKD). Animals (Basel) 2025; 15:242. [PMID: 39858242 PMCID: PMC11758669 DOI: 10.3390/ani15020242] [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] [Received: 12/04/2024] [Revised: 01/02/2025] [Accepted: 01/10/2025] [Indexed: 01/27/2025] Open
Abstract
Urine-derived mesenchymal stromal/stem cells (USCs) could be a valuable source of cells in regenerative medicine because urine can be easily collected non-invasively. In this paper, USCs were isolated from both healthy dogs and dogs affected by chronic kidney disease (CKD), and the efficacy of collection methods (spontaneous micturition, bladder catheterization, and cystocentesis) were compared. Isolated cells were cultured in the presence of platelet-rich plasma and studied for their proliferative capacity (growth curve, doubling time, and colony forming unit), differentiation properties, expression of mesenchymal markers, and Klotho protein. Morphologically, all cells were elongated and fibroblast-like. USCs isolated from samples collected by spontaneous micturition and bladder catheterization failed to proliferate, whilst USCs obtained by cystocentesis showed a doubling time of 2.04 days in healthy dogs and 1.7 days in dogs with CKD (p < 0.05). Cells were able to differentiate into osteogenic, chondrogenic, and adipogenic lines, showed positive expression to mesenchymal/stem markers, negative expression to hematopoietic markers, and major histocompatibility complex (MHCII) antigen. Klotho protein expression was confirmed. This study confirmed that USCs from healthy and CKD dogs can act as stem cells, with those from sick dogs having greater proliferative ability with the potential for use as autologous therapies.
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Affiliation(s)
- Anna Lange-Consiglio
- Reproduction Laboratory, Department of Veterinary Medicine and Animal Science, Università degli Studi di Milano, 26900 Lodi, Italy; (A.L.-C.); (F.C.)
| | - Filippo Tagliasacchi
- Department of Veterinary Medicine and Animal Science, Università degli Studi di Milano, 26900 Lodi, Italy; (F.T.); (C.G.); (C.P.); (P.S.); (P.R.)
| | - Fausto Cremonesi
- Reproduction Laboratory, Department of Veterinary Medicine and Animal Science, Università degli Studi di Milano, 26900 Lodi, Italy; (A.L.-C.); (F.C.)
| | - Claudia Gusmara
- Department of Veterinary Medicine and Animal Science, Università degli Studi di Milano, 26900 Lodi, Italy; (F.T.); (C.G.); (C.P.); (P.S.); (P.R.)
- Laboratorio di Malattie Infettive degli Animali (MiLab), Department of Veterinary Medicine and Animal Science, Università degli Studi di Milano, 26900 Lodi, Italy
| | - Claudia Pollera
- Department of Veterinary Medicine and Animal Science, Università degli Studi di Milano, 26900 Lodi, Italy; (F.T.); (C.G.); (C.P.); (P.S.); (P.R.)
| | - Paola Scarpa
- Department of Veterinary Medicine and Animal Science, Università degli Studi di Milano, 26900 Lodi, Italy; (F.T.); (C.G.); (C.P.); (P.S.); (P.R.)
| | - Giulia Gaspari
- Reproduction Laboratory, Department of Veterinary Medicine and Animal Science, Università degli Studi di Milano, 26900 Lodi, Italy; (A.L.-C.); (F.C.)
| | - Pietro Riccaboni
- Department of Veterinary Medicine and Animal Science, Università degli Studi di Milano, 26900 Lodi, Italy; (F.T.); (C.G.); (C.P.); (P.S.); (P.R.)
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Yuan Q, Wang Y, Hu S, Cai Z, Jiang L, Huang Y. Role of microRNA in Diabetic Osteoporosis. Mol Biotechnol 2024:10.1007/s12033-024-01316-1. [PMID: 39609335 DOI: 10.1007/s12033-024-01316-1] [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] [Received: 08/14/2024] [Accepted: 10/25/2024] [Indexed: 11/30/2024]
Abstract
Diabetic osteoporosis (DOP), a complication associated with diabetes mellitus (DM), is a metabolic bone disorder characterized by a reduction in bone mass per unit volume, impaired bone tissue microarchitecture, heightened bone fragility, and increased susceptibility to fractures. Individuals with diabetes exhibit a significantly greater incidence of osteoporosis and related fractures than those without diabetes. These fractures present a significant challenge in terms of the healing process and can result in severe consequences, including fatalities. MicroRNAs (miRNAs), a class of noncoding RNAs, play a pivotal role in numerous human diseases and are implicated in the pathogenesis of DOP. This review initially elucidates the essential role of miRNAs in the pathogenesis of DOP. Next, we emphasize the potential significance of miRNAs as valuable biomarkers for diagnosing DOP and predicting DOP-related fractures. Furthermore, we explore the involvement of miRNAs in managing DOP through various pathways, including conventional pharmaceutical interventions and exercise therapy. Importantly, miRNAs exhibit potential as targeted therapeutic agents for effectively treating DOP. Finally, we highlight the use of novel materials and exosomes for miRNA delivery, which has significant advantages in the treatment of DOP and overcomes the limitations associated with miRNA delivery.
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Affiliation(s)
- Qiong Yuan
- Department of Transfusion, The Affiliated Hospital, Southwest Medical University, Taiping Road 25#, Jiang Yang District, Luzhou, 646000, Sichuan, China
- Department of Transfusion, Zigong First People's Hospital, Zigong, 643000, China
| | - Yuhan Wang
- Department of Clinical Laboratory, Luzhou Longmatan District People's Hospital, Luzhou, 646000, China
| | - Shan Hu
- Department of Transfusion, Guanghan People's Hospital, Deyang, 618300, China
| | - Zhi Cai
- Department of Transfusion, The Affiliated Hospital, Southwest Medical University, Taiping Road 25#, Jiang Yang District, Luzhou, 646000, Sichuan, China
| | - Ling Jiang
- Department of Transfusion, The Affiliated Hospital, Southwest Medical University, Taiping Road 25#, Jiang Yang District, Luzhou, 646000, Sichuan, China
| | - Yuanshuai Huang
- Department of Transfusion, The Affiliated Hospital, Southwest Medical University, Taiping Road 25#, Jiang Yang District, Luzhou, 646000, Sichuan, China.
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Atia GA, Rashed F, Taher ES, Cho SG, Dayem AA, Soliman MM, Shalaby HK, Mohammed NA, Taymour N, El-Sherbiny M, Ebrahim E, Ramadan MM, Abdelkader A, Abdo M, Aldarmahi AA, Atwa AM, Bafail DA, Abdeen A. Challenges of therapeutic applications and regenerative capacities of urine based stem cells in oral, and maxillofacial reconstruction. Biomed Pharmacother 2024; 177:117005. [PMID: 38945084 DOI: 10.1016/j.biopha.2024.117005] [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: 03/31/2024] [Revised: 06/09/2024] [Accepted: 06/17/2024] [Indexed: 07/02/2024] Open
Abstract
Urine-derived stem cells (USCs) have gained the attention of researchers in the biomedical field in the past few years . Regarding the several varieties of cells that have been used for this purpose, USCs have demonstrated mesenchymal stem cell-like properties, such as differentiation and immunomodulation. Furthermore, they could be differentiated into several lineages. This is very interesting for regenerative techniques based on cell therapy. This review will embark on describing their separation, and profiling. We will specifically describe the USCs characteristics, in addition to their differentiation potential. Then, we will introduce and explore the primary uses of USCs. These involve thier utilization as a platform to produce stem cells, however, we shall concentrate on the utilization of USCs for therapeutic, and regenerative orofacial applications, providing an in-depth evaluation of this purpose. The final portion will address the limitations and challenges of their implementation in regenerative dentistry.
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Affiliation(s)
- Gamal A Atia
- Department of Oral Medicine, Periodontology, and Diagnosis, Faculty of Dentistry, Suez Canal University, Ismailia 41522, Egypt.
| | - Fatema Rashed
- Department of Basic Medical and Dental Sciences, Faculty of Dentistry, Zarqa University, Zarqa 13110, Jordan
| | - Ehab S Taher
- Department of Basic Medical and Dental Sciences, Faculty of Dentistry, Zarqa University, Zarqa 13110, Jordan
| | - Ssang-Goo Cho
- Department of Stem Cell and Regenerative Biotechnology and Institute of Advanced Regenerative Science, Konkuk University, Seoul 05029, South Korea.
| | - Ahmed Abdal Dayem
- Department of Stem Cell and Regenerative Biotechnology and Institute of Advanced Regenerative Science, Konkuk University, Seoul 05029, South Korea
| | - Magdalen M Soliman
- Department of Oral Medicine, Periodontology, and Diagnosis, Faculty of Dentistry, Badr University, Egypt
| | - Hany K Shalaby
- Department of Oral Medicine, Periodontology and Oral Diagnosis, Faculty of Dentistry, Suez University, Suez 43512, Egypt
| | - Nourelhuda A Mohammed
- Physiology and Biochemistry Department, Faculty of Medicine, Mutah University, Mutah, Al-Karak 61710, Jordan
| | - Noha Taymour
- Department of Substitutive Dental Sciences, College of Dentistry, Imam Abdulrahman Bin Faisal University, P.O. Box 1982, Dammam 31441, Saudi Arabia
| | - Mohamed El-Sherbiny
- Department of Basic Medical Sciences, College of Medicine, AlMaarefa University, 71666, Riyadh 11597, Saudi Arabia; Department of Anatomy, Faculty of Medicine, Mansoura University, Mansoura 35516, Egypt
| | - Elturabi Ebrahim
- Department of Medical Surgical Nursing, Nursing College, Prince Sattam bin Abdulaziz University, Al-Kharj 11942, Saudi Arabia
| | - Mahmoud M Ramadan
- Department of Clinical Sciences, College of Medicine, University of Sharjah, Sharjah 27272, United Arab Emirates
| | - Afaf Abdelkader
- Department of Forensic Medicine and Clinical Toxicology, Faculty of Medicine, Benha University, Benha 13518, Egypt
| | - Mohamed Abdo
- Department of Animal Histology and Anatomy, School of Veterinary Medicine, Badr University in Cairo (BUC), Badr City, Egypt; Department of Anatomy and Embryology, Faculty Veterinary Medicine, University of Sadat City, Sadat City, Egypt
| | - Ahmed A Aldarmahi
- Department of Basic Science, College of Science and Health Professions, King Saud bin Abdulaziz University for Health Sciences, Jeddah 21582, Saudi Arabia; National Guard, Health Affairs, King Abdullah International Medical Research Centre, Jeddah 21582, Saudi Arabia
| | - Ahmed M Atwa
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, Egyptian Russian University, Cairo 11829, Egypt
| | - Duaa A Bafail
- Department of Clinical Pharmacology, Faculty of Medicine, King Abdulaziz University, Jeddah 11829, Saudi Arabia
| | - Ahmed Abdeen
- Department of Forensic Medicine and Toxicology, Faculty of Veterinary Medicine, Benha University, Toukh 13736, Egypt.
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Zhang LC, Li N, Chen JL, Sun J, Xu M, Liu WQ, Zuo ZF, Shi LL, Wang TH, Luo XY. Molecular network mechanism in cerebral ischemia-reperfusion rats treated with human urine stem cells. Heliyon 2024; 10:e27508. [PMID: 38560254 PMCID: PMC10979071 DOI: 10.1016/j.heliyon.2024.e27508] [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: 04/21/2023] [Revised: 02/28/2024] [Accepted: 02/29/2024] [Indexed: 04/04/2024] Open
Abstract
Objective To explore the effect of human urine-derived stem cells (husc) in improving the neurological function of rats with cerebral ischemia-reperfusion (CIR), and report new molecular network by bioinformatics, combined with experiment validation. Methods After CIR model was established, and husc were transplanted into the lateral ventricle of rats，neurological severe score (NSS) andgene network analysis were performed. Firstly, we input the keywords "Cerebral reperfusion" and "human urine stem cells" into Genecard database and merged data with findings from PubMed so as to get their targets genes, and downloaded them to make Venny intersection plot. Then, Gene ontology (GO) analysis, kyoto encyclopedia of genes and genomes (KEGG) pathway analysis and protein-protein interaction (PPI) were performed to construct molecular network of core genes. Lastly, the expressional level of core genes was validated via quantitative real-time polymerase chain reaction (qRT-PCR), and localized by immunofluorescence. Results Compared with the Sham group, the neurological function of CIR rats was significantly improved after the injection of husc into the lateral ventricle; at 14 days, P = 0.028, which was statistically significant. There were 258 overlapping genes between CIR and husc, and integrated with 252 genes screened from PubMed and CNKI. GO enrichment analysis were mainly involved neutrophil degranulation, neutrophil activation in immune response and platelet positive regulation of degranulation, Hemostasis, blood coagulation, coagulation, etc. KEGG pathway analysis was mainly involved in complement and coagulation cascades, ECM-receptor. Hub genes screened by Cytoscape consist ofCD44, ACTB, FN1, ITGB1, PLG, CASP3, ALB, HSP90AA1, EGF, GAPDH. Lastly, qRT-PCR results showed statistic significance (P < 0.05) in ALB, CD44 and EGF before and after treatment, and EGF immunostaining was localized in neuron of cortex. Conclusion husc transplantation showed a positive effect in improving neural function of CIR rats, and underlying mechanism is involved in CD44, ALB, and EGF network.
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Affiliation(s)
- Lang-Chun Zhang
- Department of Neurosurgery, Xiang Ya Hospital of Central South University, Changsha, 410078, China
- Animal Canter Department of Anatomy, Kunming Medical University, Kunming, 650500, China
| | - Na Li
- Animal Canter Department of Anatomy, Kunming Medical University, Kunming, 650500, China
| | - Ji-Lin Chen
- Animal Canter Department of Anatomy, Kunming Medical University, Kunming, 650500, China
| | - Jie Sun
- Animal Canter Department of Anatomy, Kunming Medical University, Kunming, 650500, China
| | - Min Xu
- Animal Canter Department of Anatomy, Kunming Medical University, Kunming, 650500, China
| | - Wen-Qiang Liu
- College of Basic Medicine, Jinzhou Medical University, Jinzhou, 121000, China
| | - Zhong-Fu Zuo
- Department of Anatomy, Jinzhou Medical University, Jinzhou, China
| | - Lan-Lan Shi
- Department of Neurosurgery, Xiang Ya Hospital of Central South University, Changsha, 410078, China
| | - Ting-Hua Wang
- Department of Neurosurgery, Xiang Ya Hospital of Central South University, Changsha, 410078, China
| | - Xiang-Yin Luo
- Department of Neurosurgery, Xiang Ya Hospital of Central South University, Changsha, 410078, China
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Qiao Y, Shen L, Zhang Y, Zhou M, Sun Z. Boldine promotes stemness of human urine-derived stem cells by activating the Wnt/β-catenin signaling pathway. Mol Cell Biochem 2024; 479:243-254. [PMID: 37036633 DOI: 10.1007/s11010-023-04721-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2023] [Accepted: 03/22/2023] [Indexed: 04/11/2023]
Abstract
Human urine-derived stem cells (hUSCs) process self-renewal and multilineage differentiation ability. Due to their non-invasive and easily available clinical source, hUSCs represent a promising alternative source of mesenchymal stem cells (MSCs) for application potential in cytotherapy. However, technical limitations, such as stemness property maintenance, have hindered hUSCs' clinical application. Certain some small molecules have been recognized with advantage in maintaining the stemness of stem cells. In this study, we identified stemness-regulated key targets of hUSCs based on the StemCellNet database, CMAP database and literature mining. Furthermore, we identified a small molecule compound, boldine, which may have the potential to promote the stemness of hUSCs. It promotes cell proliferation, multilineage differentiation and maintains stemness of hUSCs by cell viability assay, single-cell clone formation, osteogenic differentiation and stemness marker expression (OCT-4 and C-MYC). We identified that boldine may be a potential GSK-3β inhibitor by molecular docking and confirmed that it can upregulate the level of β-catenin and promote translocation of β-catenin into nucleus of hUSCs using Western blotting and immunofluorescence analysis. Our study indicates boldine activates the Wnt/β-catenin signaling pathway in hUSCs and provides an effective strategy for MSCs research and application of small molecules in maintaining the stemness of hUSCs.
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Affiliation(s)
- Yinggu Qiao
- School of Life Sciences, Beijing University of Chinese Medicine, Beijing, 102488, China
| | - Liangliang Shen
- School of Life Sciences, Beijing University of Chinese Medicine, Beijing, 102488, China
| | - Yixue Zhang
- School of Life Sciences, Beijing University of Chinese Medicine, Beijing, 102488, China
| | - Ming Zhou
- School of Life Sciences, Beijing University of Chinese Medicine, Beijing, 102488, China
| | - Zhenxiao Sun
- School of Life Sciences, Beijing University of Chinese Medicine, Beijing, 102488, China.
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Zhang D, Du J, Yu M, Suo L. Urine-derived stem cells-extracellular vesicles ameliorate diabetic osteoporosis through HDAC4/HIF-1α/VEGFA axis by delivering microRNA-26a-5p. Cell Biol Toxicol 2023; 39:2243-2257. [PMID: 35554780 DOI: 10.1007/s10565-022-09713-5] [Citation(s) in RCA: 17] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2021] [Accepted: 04/07/2022] [Indexed: 11/09/2022]
Abstract
Critical roles of stem cell-extracellular vesicles (EVs) in the management of osteoporosis have been documented. Here, this study was designed to enlarge the research of the specific effects and underlying mechanism of urine-derived stem cells-EVs (USCs-EVs) on osteoporosis in diabetes rats. Firstly, miR-26a-5p and histone deacetylase 4 (HDAC4) expression in USCs of rats after diabetic osteoporosis (DOP) modeling induced by streptozotocin injection was determined, followed by study of their interaction. Then, USCs-EVs were co-cultured with osteogenic precursor cells, the effects of miRNA-26a-5p (miR-26a-5p) on osteoblasts, osteoclasts, bone mineralization deposition rate were evaluated. Meanwhile, the effect of USCs-EVs carrying miR-26a-5p on DOP rats was assessed. Elevated miR-26a-5p was seen in USCs-EVs which limited HDAC4 expression. Moreover, USCs-EVs delivered miR-26a-5p to osteogenic precursor cells, thereby promoting their differentiation, enhancing the activity of osteoblasts, and inhibiting the activity of osteoclasts, thereby preventing DOP through the activation of hypoxia inducible factor 1 subunit alpha (HIF-1α)/vascular endothelial growth factor A (VEGFA) pathway by repressing HDAC4. In a word, USCs-EVs-miR-26a-5p is a promising therapy for DOP by activating HIF-1α/VEGFA pathway through HDAC4 inhibition. 1. USCs-EVs-miR-26a-5p targeted HDAC4 and limited HDAC4 expression. 2. miR-26a-5p was delivered by USCs-EVs into osteoblast precursor cells. 3. USCs-EVs-miR-26a-5p promoted the differentiation of osteoblast precursor cells into osteoblasts. 4. miR-26a-5p delivered by USCs-EVs could inhibit HDAC4. 5. USCs-EVs-miR-26a-5p could prevent the pathogenesis of DOP via HIF-1α/VEGFA aix.
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Affiliation(s)
- Dan Zhang
- Department of Endocrinology, The Fourth Affiliated Hospital of China Medical University, Shenyang, 110032, People's Republic of China
| | - Jian Du
- Department of Endocrinology, The Fourth Affiliated Hospital of China Medical University, Shenyang, 110032, People's Republic of China
| | - Min Yu
- Department of Cell Biology, Key Laboratory of Cell Biology, Ministry of Public Health, and Key Laboratory of Medical Cell Biology, Ministry of Education, China Medical University, Shenyang, 110122, China
| | - Linna Suo
- Department of Endocrinology, The Fourth Affiliated Hospital of China Medical University, Shenyang, 110032, People's Republic of China.
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Meng F, Liao X, Chen H, Deng S, Wang L, Zhao M, Li H, Liu D, Gao G, Li H, Wang J. Bibliometric and visualization analysis of literature relating to diabetic erectile dysfunction. Front Endocrinol (Lausanne) 2022; 13:1091999. [PMID: 36568113 PMCID: PMC9780376 DOI: 10.3389/fendo.2022.1091999] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/07/2022] [Accepted: 11/28/2022] [Indexed: 12/13/2022] Open
Abstract
Introduction Diabetic erectile dysfunction (DMED) refers to erectile dysfunction secondary to diabetes. Erectile dysfunction is characterized by a persistent inability to achieve and maintain an erection sufficient to permit satisfactory sexual activity. Methods Based on the Web of Science core collection database, we firstly analyzed the quantity and quality of publications in the field of DMED, secondly profiled the publishing groups in terms of country, institution, author's publication and cooperation network, and finally sorted out and summarized the hot topics of research. Results From 2001 to 2022, a total of 1,403 articles relating to this topic were published in 359 journals. They represent the global research status, potential hotspots, and future research directions. The number of DMED-related publications and citations has steadily increased over the few past decades. Academic institutions from Europe and the United States have played a leading role in DMED research. The country, institution, journal, and author with the most publications were the United States (294), INHA University (39), the Journal of Sexual Medicine (156), and Ryu, Ji-Kan (29), respectively. The most common keywords were erectile dysfunction (796), men (256), diabetes (254), diabetes mellitus (239), prevalence (180), corpus cavernosum (171), dysfunction (155), mellitus (154), nitric-oxide synthase (153), and expression (140). The main keyword-based research topics and hotspots in the DMED field were oral sildenafil, smooth muscle relaxation, nitric oxide synthase, gene therapy, metabolic syndrome, cavernous nerve injury, stem cell, and penile prosthesis. Discussion The terms oral sildenafil, smooth muscle relaxation, nitric oxide synthase, gene therapy, metabolic syndrome, cavernous nerve injury, stem cell, and penile prosthesis will be at the forefront of DMED-related research.
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Affiliation(s)
- Fanchao Meng
- Urology Surgery, The Third Affiliated Hospital of Beijing University of Chinese Medicine, Beijing, China
| | - Xiaoxing Liao
- Urology Surgery, The Third Affiliated Hospital of Beijing University of Chinese Medicine, Beijing, China
| | - Haimin Chen
- Department of Nephroendocrinology, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, China
| | - Sheng Deng
- Department of Andrology, Shunyi Hospital, Beijing Hospital of Traditional Chinese Medicine, Beijing, China
| | - Lu Wang
- Department of Surgery, Beijing Xuanwu Traditional Chinese Medicine Hospital, Beijing, China
| | - Mengjie Zhao
- Urology Surgery, The Third Affiliated Hospital of Beijing University of Chinese Medicine, Beijing, China
| | - Haibin Li
- Urology Surgery, The Third Affiliated Hospital of Beijing University of Chinese Medicine, Beijing, China
| | - Dong Liu
- Urology Surgery, The Third Affiliated Hospital of Beijing University of Chinese Medicine, Beijing, China
| | - Guojing Gao
- Urology Surgery, The Third Affiliated Hospital of Beijing University of Chinese Medicine, Beijing, China
| | - Haisong Li
- Department of Andrology, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, China
| | - Jisheng Wang
- Department of Andrology, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, China
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Najafi-Ghalehlou N, Feizkhah A, Mobayen M, Pourmohammadi-Bejarpasi Z, Shekarchi S, Roushandeh AM, Roudkenar MH. Plumping up a Cushion of Human Biowaste in Regenerative Medicine: Novel Insights into a State-of-the-Art Reserve Arsenal. Stem Cell Rev Rep 2022; 18:2709-2739. [PMID: 35505177 PMCID: PMC9064122 DOI: 10.1007/s12015-022-10383-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 04/25/2022] [Indexed: 12/03/2022]
Abstract
Major breakthroughs and disruptive methods in disease treatment today owe their thanks to our inch by inch developing conception of the infinitive aspects of medicine since the very beginning, among which, the role of the regenerative medicine can on no account be denied, a branch of medicine dedicated to either repairing or replacing the injured or diseased cells, organs, and tissues. A novel means to accomplish such a quest is what is being called "medical biowaste", a large assortment of biological samples produced during a surgery session or as a result of physiological conditions and biological activities. The current paper accentuating several of a number of promising sources of biowaste together with their plausible applications in routine clinical practices and the confronting challenges aims at inspiring research on the existing gap between clinical and basic science to further extend our knowledge and understanding concerning the potential applications of medical biowaste.
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Affiliation(s)
- Nima Najafi-Ghalehlou
- Department of Medical Laboratory Sciences, Faculty of Paramedicine, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Alireza Feizkhah
- Burn and Regenerative Medicine Research Center, School of Medicine, Velayat Hospital, Guilan University of Medical Sciences, Rasht, Iran
| | - Mohammadreza Mobayen
- Burn and Regenerative Medicine Research Center, School of Medicine, Velayat Hospital, Guilan University of Medical Sciences, Rasht, Iran
| | - Zahra Pourmohammadi-Bejarpasi
- Burn and Regenerative Medicine Research Center, School of Medicine, Velayat Hospital, Guilan University of Medical Sciences, Rasht, Iran
| | - Shima Shekarchi
- Anatomical Sciences Department, School of Medicine, Guilan University of Medical Sciences, Rasht, Iran
| | - Amaneh Mohammadi Roushandeh
- Burn and Regenerative Medicine Research Center, School of Medicine, Velayat Hospital, Guilan University of Medical Sciences, Rasht, Iran.
| | - Mehryar Habibi Roudkenar
- Burn and Regenerative Medicine Research Center, School of Medicine, Velayat Hospital, Guilan University of Medical Sciences, Rasht, Iran.
- Cardiovascular Diseases Research Center, Department of Cardiology, School of Medicine, Heshmat Hospital, Guilan University of Medical Sciences, Rasht, Iran.
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Xia Y, Yang R, Hou Y, Wang H, Li Y, Zhu J, Fu C. Application of mesenchymal stem cell-derived exosomes from different sources in intervertebral disc degeneration. Front Bioeng Biotechnol 2022; 10:1019437. [PMID: 36277386 PMCID: PMC9585200 DOI: 10.3389/fbioe.2022.1019437] [Citation(s) in RCA: 33] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/15/2022] [Accepted: 09/26/2022] [Indexed: 12/12/2022] Open
Abstract
Intervertebral disc degeneration (IVDD) is a main cause of lower back pain, leading to psychological and economic burdens to patients. Physical therapy only delays pain in patients but cannot eliminate the cause of IVDD. Surgery is required when the patient cannot tolerate pain or has severe neurological symptoms. Although surgical resection of IVD or decompression of the laminae eliminates the diseased segment, it damages adjacent normal IVD. There is also a risk of re-protrusion after IVD removal. Cell therapy has played a crucial role in the development of regenerative medicine. Cell transplantation promotes regeneration of degenerative tissue. However, owing to the lack of vascular structure in IVD, sufficient nutrients cannot be provided for transplanted mesenchymal stem cells (MSCs). In addition, dead cells release harmful substances that aggravate IVDD. Extracellular vesicles (EVs) have been extensively studied as an emerging therapeutic approach. EVs generated by paracrine MSCs retain the potential of MSCs and serve as carriers to deliver their contents to target cells to regulate target cell activity. Owing to their double-layered membrane structure, EVs have a low immunogenicity and no immune rejection. Therefore, EVs are considered an emerging therapeutic modality in IVDD. However, they are limited by mass production and low loading rates. In this review, the structure of IVD and advantages of EVs are introduced, and the application of MSC-EVs in IVDD is discussed. The current limitations of EVs and future applications are described.
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Affiliation(s)
- Yuanliang Xia
- Department of Spine Surgery, The First Hospital of Jilin University, Changchun, China
| | - Ruohan Yang
- Cancer Center, The First Hospital of Jilin University, Changchun, China
| | - Yulin Hou
- Department of Cardiology, Guangyuan Central Hospital, Guangyuan, China
| | - Hengyi Wang
- Department of Spine Surgery, The First Hospital of Jilin University, Changchun, China
| | - Yuehong Li
- Department of Spine Surgery, The First Hospital of Jilin University, Changchun, China
| | - Jianshu Zhu
- Department of Spine Surgery, The First Hospital of Jilin University, Changchun, China
| | - Changfeng Fu
- Department of Spine Surgery, The First Hospital of Jilin University, Changchun, China
- *Correspondence: Changfeng Fu,
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Chen C, Shi Q, Li M, Chen Y, Zhang T, Xu Y, Liao Y, Ding S, Wang Z, Li X, Zhao C, Sun L, Hu J, Lu H. Engineering an enthesis-like graft for rotator cuff repair: An approach to fabricate highly biomimetic scaffold capable of zone-specifically releasing stem cell differentiation inducers. Bioact Mater 2022; 16:451-471. [PMID: 35386315 PMCID: PMC8965727 DOI: 10.1016/j.bioactmat.2021.12.021] [Citation(s) in RCA: 26] [Impact Index Per Article: 8.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2021] [Revised: 11/29/2021] [Accepted: 12/19/2021] [Indexed: 02/09/2023] Open
Abstract
Rotator cuff (RC) attaches to humerus across a triphasic yet continuous tissue zones (bone-fibrocartilage-tendon), termed "enthesis". Regrettably, rapid and functional enthesis regeneration is challenging after RC tear. The existing grafts bioengineered for RC repair are insufficient, as they were engineered by a scaffold that did not mimic normal enthesis in morphology, composition, and tensile property, meanwhile cannot simultaneously stimulate the formation of bone-fibrocartilage-tendon tissues. Herein, an optimized decellularization approach based on a vacuum aspiration device (VAD) was developed to fabricate a book-shaped decellularized enthesis matrix (O-BDEM). Then, three recombinant growth factors (CBP-GFs) capable of binding collagen were synthesized by fusing a collagen-binding peptide (CBP) into the N-terminal of BMP-2, TGF-β3, or GDF-7, and zone-specifically tethered to the collagen of O-BDEM to fabricate a novel scaffold (CBP-GFs/O-BDEM) satisfying the above-mentioned requirements. After ensuring the low immunogenicity of CBP-GFs/O-BDEM by a novel single-cell mass cytometry in a mouse model, we interleaved urine-derived stem cell-sheets into this CBP-GFs/O-BDEM to bioengineer an enthesis-like graft. Its high-performance on regenerating enthesis was determined in a canine model. These findings indicate this CBP-GFs/O-BDEM may be an excellent scaffold for constructing enthesis-like graft to patch large/massive RC tears, and provide breakthroughs in fabricating graded interfacial tissue.
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Affiliation(s)
- Can Chen
- Department of Orthopedics, Xiangya Hospital, Central South University, Changsha, 410008, China
- Key Laboratory of Organ Injury, Aging and Regenerative Medicine of Hunan Province, Changsha, 410008, China
- Hunan Engineering Research Center of Sports and Health, Changsha, 410008, China
- Xiangya Hospital-International Chinese Musculoskeletal Research Society Sports Medicine Research Centre, Changsha, 410008, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China
| | - Qiang Shi
- Key Laboratory of Organ Injury, Aging and Regenerative Medicine of Hunan Province, Changsha, 410008, China
- Hunan Engineering Research Center of Sports and Health, Changsha, 410008, China
- Xiangya Hospital-International Chinese Musculoskeletal Research Society Sports Medicine Research Centre, Changsha, 410008, China
- Department of Sports Medicine, Xiangya Hospital, Central South University, Changsha, 410008, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China
| | - Muzhi Li
- Key Laboratory of Organ Injury, Aging and Regenerative Medicine of Hunan Province, Changsha, 410008, China
- Hunan Engineering Research Center of Sports and Health, Changsha, 410008, China
- Xiangya Hospital-International Chinese Musculoskeletal Research Society Sports Medicine Research Centre, Changsha, 410008, China
- Department of Rehabilitation, The Second Xiangya Hospital, Central South University, Changsha, Hunan, 410011, China
| | - Yang Chen
- Key Laboratory of Organ Injury, Aging and Regenerative Medicine of Hunan Province, Changsha, 410008, China
- Hunan Engineering Research Center of Sports and Health, Changsha, 410008, China
- Xiangya Hospital-International Chinese Musculoskeletal Research Society Sports Medicine Research Centre, Changsha, 410008, China
- Department of Sports Medicine, Xiangya Hospital, Central South University, Changsha, 410008, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China
| | - Tao Zhang
- Key Laboratory of Organ Injury, Aging and Regenerative Medicine of Hunan Province, Changsha, 410008, China
- Hunan Engineering Research Center of Sports and Health, Changsha, 410008, China
- Xiangya Hospital-International Chinese Musculoskeletal Research Society Sports Medicine Research Centre, Changsha, 410008, China
- Department of Sports Medicine, Xiangya Hospital, Central South University, Changsha, 410008, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China
| | - Yan Xu
- Key Laboratory of Organ Injury, Aging and Regenerative Medicine of Hunan Province, Changsha, 410008, China
- Hunan Engineering Research Center of Sports and Health, Changsha, 410008, China
- Xiangya Hospital-International Chinese Musculoskeletal Research Society Sports Medicine Research Centre, Changsha, 410008, China
- Department of Sports Medicine, Xiangya Hospital, Central South University, Changsha, 410008, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China
| | - Yunjie Liao
- Department of Radiology, The Third Xiangya Hospital, Central South University, Changsha, 410013, China
| | - Shulin Ding
- Key Laboratory of Organ Injury, Aging and Regenerative Medicine of Hunan Province, Changsha, 410008, China
- Hunan Engineering Research Center of Sports and Health, Changsha, 410008, China
- Xiangya Hospital-International Chinese Musculoskeletal Research Society Sports Medicine Research Centre, Changsha, 410008, China
- Department of Spine Surgery, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China
| | - Zhanwen Wang
- Key Laboratory of Organ Injury, Aging and Regenerative Medicine of Hunan Province, Changsha, 410008, China
- Hunan Engineering Research Center of Sports and Health, Changsha, 410008, China
- Xiangya Hospital-International Chinese Musculoskeletal Research Society Sports Medicine Research Centre, Changsha, 410008, China
- Department of Sports Medicine, Xiangya Hospital, Central South University, Changsha, 410008, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China
| | - Xing Li
- Key Laboratory of Organ Injury, Aging and Regenerative Medicine of Hunan Province, Changsha, 410008, China
- Hunan Engineering Research Center of Sports and Health, Changsha, 410008, China
- Xiangya Hospital-International Chinese Musculoskeletal Research Society Sports Medicine Research Centre, Changsha, 410008, China
- Department of Spine Surgery, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China
| | - Chunfeng Zhao
- Division of Orthopedic Research and Department of Orthopedic Surgery, Mayo Clinic, Rochester, Minnesota, 55905, United States
| | - Lunquan Sun
- Center for Molecular Medicine, Xiangya Hospital, Central South University, Changsha, 410008, China
| | - Jianzhong Hu
- Key Laboratory of Organ Injury, Aging and Regenerative Medicine of Hunan Province, Changsha, 410008, China
- Hunan Engineering Research Center of Sports and Health, Changsha, 410008, China
- Xiangya Hospital-International Chinese Musculoskeletal Research Society Sports Medicine Research Centre, Changsha, 410008, China
- Department of Spine Surgery, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China
- Corresponding author. Xiangya Hospital, Central South University, No. 87, Xiangya Road, Changsha, 410008, Hunan, China.
| | - Hongbin Lu
- Key Laboratory of Organ Injury, Aging and Regenerative Medicine of Hunan Province, Changsha, 410008, China
- Hunan Engineering Research Center of Sports and Health, Changsha, 410008, China
- Xiangya Hospital-International Chinese Musculoskeletal Research Society Sports Medicine Research Centre, Changsha, 410008, China
- Department of Sports Medicine, Xiangya Hospital, Central South University, Changsha, 410008, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China
- Corresponding author. Xiangya Hospital, Central South University, No. 87, Xiangya Road, Changsha, 410008, Hunan, China.
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11
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Zhang S, Li J, Li C, He J, Ling F, Liu G. Isolation and identification of a mesenchymal stem/stromal cell-like population from pediatric urethral tissue. In Vitro Cell Dev Biol Anim 2022; 58:503-511. [PMID: 35817989 DOI: 10.1007/s11626-022-00697-4] [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: 12/09/2021] [Accepted: 03/23/2022] [Indexed: 11/25/2022]
Abstract
Mesenchymal stem cells (MSCs) are important seed cells for cell therapy and tissue engineering because of their multidirectional differentiation potential, high proliferative capacity, low immunogenicity, and immunomodulatory ability. In this study, we successfully isolated and cultured a population of mesenchymal stem-like cells from pediatric urethra (PU-MSLCs). The cells had a spindle-shaped fibroblast-like morphology, similar to MSCs derived from other tissues. The PU-MSLCs highly expressed MSC surface markers CD29, CD73, CD90, and CD105 but were negative for leukocyte common antigen CD45, and MHC class II-encoded molecule HLA-DR. After in vitro induction, the PU-MSLCs had the potential to differentiate into adipocytes, osteocytes, and chondrocytes. The PU-MSLCs maintained a normal karyotype and showed no tumorigenicity during long-term cultivation. We thus demonstrated that the mesenchymal stem/stromal cell-like population obtained from pediatric urethra tissue is capable of self-renewal and multidirectional differentiation, has promising application prospects for cell therapy and tissue engineering, and is expected to contribute to urethral tissue reconstruction.
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Affiliation(s)
- Shilin Zhang
- Department of Urology, Child Healthcare Hospital, Southern Medical University, Chancheng District, Affiliated Foshan Maternity &No.11, Renmin West Road, 528000, Foshan, Guangdong, China.
| | - Jierong Li
- Department of Urology, Child Healthcare Hospital, Southern Medical University, Chancheng District, Affiliated Foshan Maternity &No.11, Renmin West Road, 528000, Foshan, Guangdong, China
| | - Chunjing Li
- Department of Urology, Child Healthcare Hospital, Southern Medical University, Chancheng District, Affiliated Foshan Maternity &No.11, Renmin West Road, 528000, Foshan, Guangdong, China
| | - Jun He
- Department of Urology, Child Healthcare Hospital, Southern Medical University, Chancheng District, Affiliated Foshan Maternity &No.11, Renmin West Road, 528000, Foshan, Guangdong, China
| | - Fengsheng Ling
- Department of Urology, Child Healthcare Hospital, Southern Medical University, Chancheng District, Affiliated Foshan Maternity &No.11, Renmin West Road, 528000, Foshan, Guangdong, China
| | - Guoqing Liu
- Department of Urology, Child Healthcare Hospital, Southern Medical University, Chancheng District, Affiliated Foshan Maternity &No.11, Renmin West Road, 528000, Foshan, Guangdong, China
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12
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Wang HN, Rong X, Yang LM, Hua WZ, Ni GX. Advances in Stem Cell Therapies for Rotator Cuff Injuries. Front Bioeng Biotechnol 2022; 10:866195. [PMID: 35694228 PMCID: PMC9174670 DOI: 10.3389/fbioe.2022.866195] [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: 01/30/2022] [Accepted: 04/25/2022] [Indexed: 11/13/2022] Open
Abstract
Rotator cuff injury is a common upper extremity musculoskeletal disease that may lead to persistent pain and functional impairment. Despite the clinical outcomes of the surgical procedures being satisfactory, the repair of the rotator cuff remains problematic, such as through failure of healing, adhesion formation, and fatty infiltration. Stem cells have high proliferation, strong paracrine action, and multiple differentiation potential, which promote tendon remodeling and fibrocartilage formation and increase biomechanical strength. Additionally, stem cell-derived extracellular vesicles (EVs) can increase collagen synthesis and inhibit inflammation and adhesion formation by carrying regulatory proteins and microRNAs. Therefore, stem cell-based therapy is a promising therapeutic strategy that has great potential for rotator cuff healing. In this review, we summarize the advances of stem cells and stem cell-derived EVs in rotator cuff repair and highlight the underlying mechanism of stem cells and stem cell-derived EVs and biomaterial delivery systems. Future studies need to explore stem cell therapy in combination with cellular factors, gene therapy, and novel biomaterial delivery systems.
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Affiliation(s)
- Hao-Nan Wang
- School of Sport Medicine and Rehabilitation, Beijing Sport University, Beijing, China
| | - Xiao Rong
- Department of Ultrasound, West China Hospital, Sichuan University, Chengdu, China
| | - Lu-Ming Yang
- Musculoskeletal Sonography and Occupational Performance Lab, Chan Division of Occupational Science and Occupational Therapy, University of Southern California, Los Angeles, CA, United States
| | - Wei-Zhong Hua
- School of Sport Medicine and Rehabilitation, Beijing Sport University, Beijing, China
| | - Guo-Xin Ni
- School of Sport Medicine and Rehabilitation, Beijing Sport University, Beijing, China
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13
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Recchia K, Machado LS, Botigelli RC, Pieri NCG, Barbosa G, de Castro RVG, Marques MG, Pessôa LVDF, Fantinato Neto P, Meirelles FV, Souza AFD, Martins SMMK, Bressan FF. In vitro induced pluripotency from urine-derived cells in porcine. World J Stem Cells 2022; 14:231-244. [PMID: 35432738 PMCID: PMC8968213 DOI: 10.4252/wjsc.v14.i3.231] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/23/2021] [Revised: 10/11/2021] [Accepted: 02/16/2022] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND The generation of induced pluripotent stem cells (iPSC) has been a game-changer in translational and regenerative medicine; however, their large-scale applicability is still hampered by the scarcity of accessible, safe, and reproducible protocols. The porcine model is a large biomedical model that enables translational applications, including gene editing, long term in vivo and offspring analysis; therefore, suitable for both medicine and animal production.
AIM To reprogramme in vitro into pluripotency, and herein urine-derived cells (UDCs) were isolated from porcine urine.
METHODS The UDCs were reprogrammed in vitro using human or murine octamer-binding transcription factor 4 (OCT4), SRY-box2 (SOX2), Kruppel-like factor 4 (KLF4), and C-MYC, and cultured with basic fibroblast growth factor (bFGF) supplementation. To characterize the putative porcine iPSCs three clonal lineages were submitted to immunocytochemistry for alkaline phosphatase (AP), OCT4, SOX2, NANOG, TRA1 81 and SSEA 1 detection. Endogenous transcripts related to the pluripotency (OCT4, SOX2 and NANOG) were analyzed via reverse transcription quantitative real-time polymerase chain reaction in different time points during the culture, and all three lineages formed embryoid bodies (EBs) when cultured in suspension without bFGF supplementation.
RESULTS The UDCs were isolated from swine urine samples and when at passage 2 submitted to in vitro reprogramming. Colonies of putative iPSCs were obtained only from UDCs transduced with the murine factors (mOSKM), but not from human factors (hOSKM). Three clonal lineages were isolated and further cultured for at least 28 passages, all the lineages were positive for AP detection, the OCT4, SOX2, NANOG markers, albeit the immunocytochemical analysis also revealed heterogeneous phenotypic profiles among lineages and passages for NANOG and SSEA1, similar results were observed in the abundance of the endogenous transcripts related to pluripotent state. All the clonal lineages when cultured in suspension without bFGF were able to form EBs expressing ectoderm and mesoderm layers transcripts.
CONCLUSION For the first time UDCs were isolated in the swine model and reprogrammed into a pluripotent-like state, enabling new numerous applications in both human or veterinary regenerative medicine.
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Affiliation(s)
- Kaiana Recchia
- Department of Surgery, Faculty of Veterinary Medicine and Animal Sciences, University of São Paulo, Pirassununga 13635-000, São Paulo, Brazil
| | - Lucas Simões Machado
- Department of Surgery, Faculty of Veterinary Medicine and Animal Sciences, University of São Paulo, Pirassununga 13635-000, São Paulo, Brazil
| | - Ramon Cesar Botigelli
- Department of Pharmacology and Biotechnology, Institute of Bioscience, São Paulo State University, Botucatu 18618-689, São Paulo, Brazil
| | - Naira Caroline Godoy Pieri
- Department of Veterinary Medicine, Faculty of Animal Sciences and Food Engineering, University of São Paulo, Pirassununga 13635-000, São Paulo, Brazil
| | - Gabriela Barbosa
- Department of Veterinary Medicine, Faculty of Animal Sciences and Food Engineering, University of São Paulo, Pirassununga 13635-000, São Paulo, Brazil
| | | | - Mariana Groke Marques
- Embrapa Suínos e Aves, Empresa Brasileira de Pesquisa Agropecuária, Concordia 89715-899, Santa Catarina, Brazil
| | - Laís Vicari de Figueiredo Pessôa
- Department of Veterinary Medicine, Faculty of Animal Sciences and Food Engineering, University of São Paulo, Pirassununga 13635-000, São Paulo, Brazil
| | - Paulo Fantinato Neto
- Department of Veterinary Medicine, Faculty of Animal Sciences and Food Engineering, University of São Paulo, Pirassununga 13635-000, São Paulo, Brazil
| | - Flávio Vieira Meirelles
- Department of Surgery, Faculty of Veterinary Medicine and Animal Sciences, University of São Paulo, Pirassununga 13635-000, São Paulo, Brazil
- Department of Veterinary Medicine, Faculty of Animal Sciences and Food Engineering, University of São Paulo, Pirassununga 13635-000, São Paulo, Brazil
| | - Aline Fernanda de Souza
- Department of Veterinary Medicine, Faculty of Animal Sciences and Food Engineering, University of São Paulo, Pirassununga 13635-000, São Paulo, Brazil
| | | | - Fabiana Fernandes Bressan
- Department of Surgery, Faculty of Veterinary Medicine and Animal Sciences, University of São Paulo, Pirassununga 13635-000, São Paulo, Brazil
- Department of Veterinary Medicine, Faculty of Animal Sciences and Food Engineering, University of São Paulo, Pirassununga 13635-000, São Paulo, Brazil
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14
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Wu S, Chen Z, Yu X, Duan X, Chen J, Liu G, Gong M, Xing F, Sun J, Huang S, Zhou X. A sustained release of BMP2 in urine-derived stem cells enhances the osteogenic differentiation and the potential of bone regeneration. Regen Biomater 2022; 9:rbac015. [PMID: 35529046 PMCID: PMC9070791 DOI: 10.1093/rb/rbac015] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/20/2021] [Revised: 01/25/2022] [Accepted: 01/30/2022] [Indexed: 02/05/2023] Open
Abstract
Cell-based tissue engineering is one of the optimistic approaches to replace current treatments for bone defects. Urine-derived stem cells (USCs) are obtained non-invasively and become one of the promising seed cells for bone regeneration. An injectable BMP2-releasing chitosan microspheres/type I collagen hydrogel (BMP2-CSM/Col I hydrogel) was fabricated. USCs proliferated in a time-dependent fashion, spread with good extension and interconnected with each other in different hydrogels both for 2D and 3D models. BMP2 was released in a sustained mode for more than 28 days. Sustained-released BMP2 increased the ALP activities and mineral depositions of USCs in 2D culture, and enhanced the expression of osteogenic genes and proteins in 3D culture. In vivo, the mixture of USCs and BMP2-CSM/Col I hydrogels effectively enhanced bone regeneration, and the ratio of new bone volume to total bone volume was 38% after 8 weeks of implantation. Our results suggested that BMP2-CSM/Col I hydrogels promoted osteogenic differentiation of USCs in 2D and 3D culture in vitro and USCs provided a promising cell source for bone tissue engineering in vivo. As such, USCs-seeded hydrogel scaffolds are regarded as an alternative approach in the repair of bone defects.
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Affiliation(s)
- Shuang Wu
- Orthopedic Research Institute, Department of Orthopedics, West China Hospital, Sichuan University, Chengdu, 610000, China
| | - Zhao Chen
- Orthopedic Research Institute, Department of Orthopedics, West China Hospital, Sichuan University, Chengdu, 610000, China
| | - Xi Yu
- Rehabilitation Medicine Center, West China Hospital, Sichuan University, Chengdu, 610000, China
| | - Xin Duan
- Orthopedic Research Institute, Department of Orthopedics, West China Hospital, Sichuan University, Chengdu, 610000, China
| | - Jialei Chen
- Orthopedic Research Institute, Department of Orthopedics, West China Hospital, Sichuan University, Chengdu, 610000, China
| | - Guoming Liu
- Department of Orthopedics, Affiliated Hospital of Qingdao University, Qingdao, 266000, China
| | - Min Gong
- Department of Orthopedics, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, 610000, China
| | - Fei Xing
- Orthopedic Research Institute, Department of Orthopedics, West China Hospital, Sichuan University, Chengdu, 610000, China
| | - Jiachen Sun
- Orthopedic Research Institute, Department of Orthopedics, West China Hospital, Sichuan University, Chengdu, 610000, China
| | - Shishu Huang
- Orthopedic Research Institute, Department of Orthopedics, West China Hospital, Sichuan University, Chengdu, 610000, China
| | - Xiang Zhou
- Orthopedic Research Institute, Department of Orthopedics, West China Hospital, Sichuan University, Chengdu, 610000, China
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15
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Wu X, Sun W. Extracellular Vesicles Derived From Stem Cells in Intervertebral Disc Degeneration. Front Cell Dev Biol 2022; 9:793363. [PMID: 35096823 PMCID: PMC8793284 DOI: 10.3389/fcell.2021.793363] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2021] [Accepted: 12/06/2021] [Indexed: 12/16/2022] Open
Abstract
Intervertebral disc degeneration (IVDD) is the leading cause of low back pain related to degradation of cartilaginous tissues, mainly resulting from oxidative stress, cell apoptosis, and extracellular matrix degradation. Extracellular vesicles (EVs) exist in all bodily fluids and can be produced by all types of cells. Stem cell-derived EVs (SC-EVs), which are the main paracrine components of stem cells, have gained significant attention in the field of regenerative medicine. Over the past years, accumulating evidence indicates the therapeutic and diagnostic potentials of EVs in IVDD. The main mechanisms involve the induction of regenerative phenotypes, apoptosis alleviation, and immune modulation. In addition, the efficiency of SC-EVs can be enhanced by choosing appropriate donor cells and cell phenotypes, optimizing cell culture conditions, or engineering EVs to deliver drugs and targeting molecules. Given the importance and novelty of SC-EVs, we give an overview of SC-EVs and discuss the roles of SC-EVs in IVDD.
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Affiliation(s)
- Xinjie Wu
- Peking University China-Japan Friendship School of Clinical Medicine, Beijing, China.,Department of Orthopedic Surgery, China-Japan Friendship Hospital, Beijing, China
| | - Wei Sun
- Peking University China-Japan Friendship School of Clinical Medicine, Beijing, China.,Department of Orthopedic Surgery, China-Japan Friendship Hospital, Beijing, China
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16
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Zhou Q, Cheng Y, Sun F, Shen J, Nasser MI, Zhu P, Zhang X, Li Y, Yin G, Wang Y, Wu X, Zhao M. A Comprehensive Review of the Therapeutic Value of Urine-Derived Stem Cells. Front Genet 2022; 12:781597. [PMID: 35047009 PMCID: PMC8762167 DOI: 10.3389/fgene.2021.781597] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/23/2021] [Accepted: 11/30/2021] [Indexed: 12/17/2022] Open
Abstract
Stem cells possess regenerative powers and multidirectional differentiation potential and play an important role in disease treatment and basic medical research. Urine-derived stem cells (USCs) represent a newly discovered type of stem cell with biological characteristics similar to those of mesenchymal stromal cells (MSCs), including their doubling time and immunophenotype. USCs are noninvasive and can be readily obtained from voided urine and steadily cultured. Based on advances in this field, USCs and their secretions have increasingly emerged as ideal sources. USCs may play regulatory roles in the cellular immune system, oxidative stress, revascularization, apoptosis and autophagy. This review summarizes the applications of USCs in tissue regeneration and various disease treatments. Furthermore, by analysing their limitations, we anticipate the development of more feasible therapeutic strategies to promote USC-based individualized treatment.
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Affiliation(s)
- Qian Zhou
- Department of Pediatrics, The Third Xiangya Hospital, Central South University, Changsha, China
| | - Yiyu Cheng
- Department of Pediatrics, The Third Xiangya Hospital, Central South University, Changsha, China
| | - Fang Sun
- Department of Pediatrics, The Third Xiangya Hospital, Central South University, Changsha, China
| | - Jie Shen
- Department of Pediatrics, The Third Xiangya Hospital, Central South University, Changsha, China
| | - M I Nasser
- Guangdong Cardiovascular Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China
| | - Ping Zhu
- Guangdong Cardiovascular Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China
| | - Xueyan Zhang
- Department of Pediatrics, The Third Xiangya Hospital, Central South University, Changsha, China
| | - Yuxiang Li
- Department of Urology, The Third Xiangya Hospital, Central South University, Changsha, China
| | - Guangming Yin
- Department of Urology, The Third Xiangya Hospital, Central South University, Changsha, China
| | - Yuequn Wang
- The Center for Heart Development, State Key Laboratory of Development Biology of Freshwater Fish, Key Laboratory of MOE for Development Biology and Protein Chemistry, College of Life Sciences, Hunan Normal University, Changsha, China
| | - Xiushan Wu
- Guangdong Cardiovascular Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China.,The Center for Heart Development, State Key Laboratory of Development Biology of Freshwater Fish, Key Laboratory of MOE for Development Biology and Protein Chemistry, College of Life Sciences, Hunan Normal University, Changsha, China
| | - Mingyi Zhao
- Department of Pediatrics, The Third Xiangya Hospital, Central South University, Changsha, China.,Guangdong Cardiovascular Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China
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17
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Huang YZ, He T, Cui J, Jiang YL, Zeng JF, Zhang WQ, Xie HQ. Urine-Derived Stem Cells for Regenerative Medicine: Basic Biology, Applications, and Challenges. TISSUE ENGINEERING. PART B, REVIEWS 2022; 28:978-994. [PMID: 35049395 DOI: 10.1089/ten.teb.2021.0142] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
Regenerative medicine based on stem cell research has the potential to provide advanced health care for human beings. Recent studies demonstrate that stem cells in human urine can serve as an excellent source of graft cells for regenerative therapy, mainly due to simple, low-cost, and noninvasive cell isolation. These cells, termed human urine-derived stem cells (USCs), are highly expandable and can differentiate into various cell lineages. They share many biological properties with mesenchymal stem cells, such as potent paracrine effects and immunomodulation ability. The advantage of USCs has motivated researchers to explore their applications in regenerative medicine, including genitourinary regeneration, musculoskeletal repair, skin wound healing, and disease treatment. Although USCs have showed many positive outcomes in preclinical studies, and although the possible applications of USCs for animal therapy have been reported, many issues need to be addressed before clinical translation. This article provides a comprehensive review of USC biology and recent advances in their application for tissue regeneration. Challenges in the clinical translation of USC-based therapy are also discussed. Impact statement Recently, stem cells isolated from urine, referred to as urine-derived stem cells (USCs), have gained much interest in the field of regenerative medicine. Many advantages of human USCs have been found for cell-based therapy: (i) the cell isolation procedure is simple and low cost; (ii) they have remarkable proliferation ability, multidifferentiation potential, and paracrine effects; and (iii) they facilitate tissue regeneration in many animal models. With the hope to facilitate the development of USC-based therapy, we describe the current understanding of USC biology, summarize recent advances in their applications, and discuss future challenges in clinical translation.
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Affiliation(s)
- Yi-Zhou Huang
- Laboratory of Stem Cell and Tissue Engineering, Orthopedic Research Institute, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center of Biotherapy, Chengdu, China
| | - Tao He
- Laboratory of Stem Cell and Tissue Engineering, Orthopedic Research Institute, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center of Biotherapy, Chengdu, China.,Department of Breast Surgery, West China School of Medicine/West China Hospital, Sichuan University, Chengdu, China
| | - Jing Cui
- Laboratory of Stem Cell and Tissue Engineering, Orthopedic Research Institute, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center of Biotherapy, Chengdu, China
| | - Yan-Lin Jiang
- Laboratory of Stem Cell and Tissue Engineering, Orthopedic Research Institute, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center of Biotherapy, Chengdu, China
| | - Jun-Feng Zeng
- Laboratory of Stem Cell and Tissue Engineering, Orthopedic Research Institute, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center of Biotherapy, Chengdu, China
| | - Wen-Qian Zhang
- Laboratory of Stem Cell and Tissue Engineering, Orthopedic Research Institute, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center of Biotherapy, Chengdu, China
| | - Hui-Qi Xie
- Laboratory of Stem Cell and Tissue Engineering, Orthopedic Research Institute, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center of Biotherapy, Chengdu, China
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Falzarano MS, Grilli A, Zia S, Fang M, Rossi R, Gualandi F, Rimessi P, El Dani R, Fabris M, Lu Z, Li W, Mongini T, Ricci F, Pegoraro E, Bello L, Barp A, Sansone VA, Hegde M, Roda B, Reschiglian P, Bicciato S, Selvatici R, Ferlini A. RNA-seq in DMD urinary stem cells recognized muscle-related transcription signatures and addressed the identification of atypical mutations by whole-genome sequencing. HGG ADVANCES 2022; 3:100054. [PMID: 35047845 PMCID: PMC8756543 DOI: 10.1016/j.xhgg.2021.100054] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/12/2021] [Accepted: 08/18/2021] [Indexed: 12/13/2022] Open
Abstract
Urinary stem cells (USCs) are a non-invasive, simple, and affordable cell source to study human diseases. Here we show that USCs are a versatile tool for studying Duchenne muscular dystrophy (DMD), since they are able to address RNA signatures and atypical mutation identification. Gene expression profiling of DMD individuals' USCs revealed a profound deregulation of inflammation, muscle development, and metabolic pathways that mirrors the known transcriptional landscape of DMD muscle and worsens following USCs' myogenic transformation. This pathogenic transcription signature was reverted by an exon-skipping corrective approach, suggesting the utility of USCs in monitoring DMD antisense therapy. The full DMD transcript profile performed in USCs from three undiagnosed DMD individuals addressed three splicing abnormalities, which were decrypted and confirmed as pathogenic variations by whole-genome sequencing (WGS). This combined genomic approach allowed the identification of three atypical and complex DMD mutations due to a deep intronic variation and two large inversions, respectively. All three mutations affect DMD gene splicing and cause a lack of dystrophin protein production, and one of these also generates unique fusion genes and transcripts. Further characterization of USCs using a novel cell-sorting technology (Celector) highlighted cell-type variability and the representation of cell-specific DMD isoforms. Our comprehensive approach to USCs unraveled RNA, DNA, and cell-specific features and demonstrated that USCs are a robust tool for studying and diagnosing DMD.
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Affiliation(s)
- Maria S Falzarano
- Department of Medical Sciences, Unit of Medical Genetics, University of Ferrara, Ferrara 44121, Italy
| | - Andrea Grilli
- Department of Life Sciences, University of Modena and Reggio Emilia, Modena 41121, Italy
| | | | | | - Rachele Rossi
- Department of Medical Sciences, Unit of Medical Genetics, University of Ferrara, Ferrara 44121, Italy
| | - Francesca Gualandi
- Department of Medical Sciences, Unit of Medical Genetics, University of Ferrara, Ferrara 44121, Italy
| | - Paola Rimessi
- Department of Medical Sciences, Unit of Medical Genetics, University of Ferrara, Ferrara 44121, Italy
| | - Reem El Dani
- Department of Medical Sciences, Unit of Medical Genetics, University of Ferrara, Ferrara 44121, Italy
| | - Marina Fabris
- Department of Medical Sciences, Unit of Medical Genetics, University of Ferrara, Ferrara 44121, Italy
| | | | - Wenyan Li
- BGI-Shenzhen, Shenzhen 518083, China
| | | | | | - Elena Pegoraro
- ERN Neuromuscular Center, Department of Neurosciences, Unit of Neurology, University of Padua, Padua 35122, Italy
| | - Luca Bello
- ERN Neuromuscular Center, Department of Neurosciences, Unit of Neurology, University of Padua, Padua 35122, Italy
| | - Andrea Barp
- The NEMO Clinical Center, Neurorehabilitation Unit, University of Milan, Milan 20162, Italy
| | - Valeria A Sansone
- The NEMO Clinical Center, Neurorehabilitation Unit, University of Milan, Milan 20162, Italy
| | - Madhuri Hegde
- PerkinElmer Genomics, 3950 Shackleford Rd., Ste. 195, Duluth, GA 30096, USA
| | - Barbara Roda
- Stem Sel s.r.l., Bologna 40127, Italy
- Department of Chemistry "G. Ciamician," University of Bologna, Bologna 40126, Italy
| | - Pierluigi Reschiglian
- Stem Sel s.r.l., Bologna 40127, Italy
- Department of Chemistry "G. Ciamician," University of Bologna, Bologna 40126, Italy
| | - Silvio Bicciato
- Department of Life Sciences, University of Modena and Reggio Emilia, Modena 41121, Italy
| | - Rita Selvatici
- Department of Medical Sciences, Unit of Medical Genetics, University of Ferrara, Ferrara 44121, Italy
| | - Alessandra Ferlini
- Department of Medical Sciences, Unit of Medical Genetics, University of Ferrara, Ferrara 44121, Italy
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Luo DS, Li YQ, Deng ZQ, Liu GH. Progress and prospect of stem cell therapy for diabetic erectile dysfunction. World J Diabetes 2021; 12:2000-2010. [PMID: 35047115 PMCID: PMC8696650 DOI: 10.4239/wjd.v12.i12.2000] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/06/2021] [Revised: 03/18/2021] [Accepted: 10/31/2021] [Indexed: 02/06/2023] Open
Abstract
Diabetic erectile dysfunction (DED) is a common complication of diabetes mellitus, significantly impairing the quality of life of patients. The conventional clinical treatment still has limitations. Stem cells (SCs), as a type of cells with multidirectional or directional differentiation capability and sustainable self-renewal potential, are widely used in regenerative medicine and tissue engineering. With the continuous update of regenerative medicine theory and the success of animal experiments, SCs as a treatment for male erectile dysfunction, especially DED, have attracted widespread attention because of curable possibility. This review focus on the current progress in the clinical application of SC treatment for DED. Moreover, we summarize the development prospects of SCs in the field of DMED therapy.
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Affiliation(s)
- Dao-Sheng Luo
- Department of Urology, Dongguan People’s Hospital, Dongguan 523000, Guangdong Province, China
| | - Yan-Qing Li
- Reproductive Centre, Sun Yat-Sen University, The Sixth Affiliated Hospital, Guangzhou 510000, Guangdong Province, China
| | - Zhi-Quan Deng
- Department of Urology, Dongguan People’s Hospital, Dongguan 523000, Guangdong Province, China
| | - Gui-Hua Liu
- Reproductive Centre, Sun Yat-Sen University, The Sixth Affiliated Hospital, Guangzhou 510000, Guangdong Province, China
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20
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Exosomal MATN3 of Urine-Derived Stem Cells Ameliorates Intervertebral Disc Degeneration by Antisenescence Effects and Promotes NPC Proliferation and ECM Synthesis by Activating TGF- β. OXIDATIVE MEDICINE AND CELLULAR LONGEVITY 2021; 2021:5542241. [PMID: 34136064 PMCID: PMC8175180 DOI: 10.1155/2021/5542241] [Citation(s) in RCA: 41] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/05/2021] [Revised: 04/05/2021] [Accepted: 05/03/2021] [Indexed: 01/03/2023]
Abstract
Objective Low back pain (LBP) is one of the top three causes of disability in developed countries, and intervertebral disc degeneration (IDD) is a major contributor to LBP. In the process of IDD, there is a gradual decrease in nucleus pulposus cells (NPCs) and extracellular matrix (ECM). Exosomes are important exocrine mediators of stem cells that can act directly on cells for tissue repair and regeneration. In this study, we determined the antisenescence, cell proliferation promotion, and ECM modulation effects of human urine-derived stem cell (USC) exosomes (USC-exos) on degenerated intervertebral discs and explored the underlying mechanism. Methods and Materials USCs were identified by multipotent differentiation and flow cytometry for mesenchymal stem cell- (MSC-) specific surface protein markers. USC-exos were isolated from the conditioned medium of USCs by ultracentrifugation and then analyzed by transmission electron microscopy (TEM), particle size analysis, and western blotting (WB) for exosome marker proteins. The effects of USC-exos on NPC proliferation and ECM synthesis were assessed by Cell Counting Kit-8 (CCK-8), WB, and immunofluorescence (IF) analyses. The protein differences between normal and degenerative intervertebral discs were mined, and the temporal and spatial variations in matrilin-3 (MATN3) content were determined by WB and IF in the intervertebral disc tissues. The candidate molecules that mediated the function of USC-exos were screened out and confirmed by multiple assays. Meanwhile, the mechanism underlying the candidate protein in USC-exos-induced cell proliferation and regulation of ECM synthesis promoting the activities of NPCs was explored. In addition, the effects of USC-exos on ameliorating intervertebral disc degeneration (IVD) in mice were examined by assessing computed tomography (CT), magnetic resonance imaging (MRI), and histological analyses. Results The flow cytometry results showed that USCs were positive for CD29, CD44, and CD73, which are USC surface-specific markers, but negative for CD34 and CD45. In addition, USCs showed osteogenic, adipogenic, and chondrogenic differentiation potential. USC-exos exhibited a cup-shaped morphology, with a mean diameter of 49.7 ± 7.3 nm, and were positive for CD63 and TSG101 and negative for calnexin. USC-exos could promote NPC proliferation and ECM synthesis. The protein content of the matrilin family was significantly reduced in degenerative intervertebral discs, and the decrease in MATN3 was the most significant. USC-exos were found to be rich in MATN3 protein, and exosomal MATN3 was required for USC-exos-induced promotion of NPC proliferation and ECM synthesis, as well as alleviation of intervertebral disc degeneration in IVD rats. In addition, the effects of MATN3 in USC-exos were demonstrated to be achieved by activating TGF-β, which elevated the phosphorylation level of SMAD and AKT. Conclusions Our study suggests that reduced MATN3 can be considered a characteristic of intervertebral disc degeneration. USC-exos may represent a potentially effective agent for alleviating intervertebral disc degeneration by promoting NPC proliferation and ECM synthesis by transferring the MATN3 protein.
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21
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Vado Y, Puras G, Rosique M, Martin C, Pedraz JL, Jebari-Benslaiman S, de Pancorbo MM, Zarate J, Perez de Nanclares G. Design and Validation of a Process Based on Cationic Niosomes for Gene Delivery into Novel Urine-Derived Mesenchymal Stem Cells. Pharmaceutics 2021; 13:pharmaceutics13050696. [PMID: 34064902 PMCID: PMC8151286 DOI: 10.3390/pharmaceutics13050696] [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: 03/30/2021] [Revised: 04/29/2021] [Accepted: 05/06/2021] [Indexed: 11/16/2022] Open
Abstract
Background: Mesenchymal stem cells (MSCs) are stem cells present in adult tissues. They can be cultured, have great growth capacity, and can differentiate into several cell types. The isolation of urine-derived mesenchymal stem cells (hUSCs) was recently described. hUSCs present additional benefits in the fact that they can be easily obtained noninvasively. Regarding gene delivery, nonviral vectors based on cationic niosomes have been used and are more stable and have lower immunogenicity than viral vectors. However, their transfection efficiency is low and in need of improvement. Methods: We isolated hUSCs from urine, and the cell culture was tested and characterized. Different cationic niosomes were elaborated using reverse-phase evaporation, and they were physicochemically characterized. Then, they were screened into hUSCs for transfection efficiency, and their internalization was evaluated. Results: GPxT-CQ at a lipid/DNA ratio of 5:1 (w/w) had the best transfection efficiency. Intracellular localization studies confirmed that nioplexes entered mainly via caveolae-mediated endocytosis. Conclusions: In conclusion, we established a protocol for hUSC isolation and their transfection with cationic niosomes, which could have relevant clinical applications such as in gene therapy. This methodology could also be used for creating cellular models for studying and validating pathogenic genetic variants, and even for performing functional studies. Our study increases knowledge about the internalization of tested cationic niosomes in these previously unexplored cells.
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Affiliation(s)
- Yerai Vado
- NanoBioCel Research Group, Laboratory of Pharmacy and Pharmaceutical Technology, Faculty of Pharmacy, University of the Basque Country UPV/EHU, 01006 Vitoria-Gasteiz, Araba, Spain; (Y.V.); (G.P.); (J.L.P.); (J.Z.)
- Rare Diseases Research Group, Molecular (Epi) Genetics Laboratory, BioAraba Health Research Institute, Araba University Hospital-Txagorritxu, 01009 Vitoria-Gasteiz, Araba, Spain
| | - Gustavo Puras
- NanoBioCel Research Group, Laboratory of Pharmacy and Pharmaceutical Technology, Faculty of Pharmacy, University of the Basque Country UPV/EHU, 01006 Vitoria-Gasteiz, Araba, Spain; (Y.V.); (G.P.); (J.L.P.); (J.Z.)
| | - Melania Rosique
- BIOMICs Research Group, Microfluidics Cluster UPV/EHU, Lascaray Research Center, University of the Basque Country UPV/EHU, 01009 Vitoria-Gasteiz, Araba, Spain; (M.R.); (M.M.d.P.)
| | - Cesar Martin
- Biofisika Institute (UPV/EHU, CSIC), Department Biochemistry and Molecular Biology, University of the Basque Country University (UPV/EHU), 48940 Leioa, Bizkaia, Spain; (C.M.); (S.J.-B.)
| | - Jose Luis Pedraz
- NanoBioCel Research Group, Laboratory of Pharmacy and Pharmaceutical Technology, Faculty of Pharmacy, University of the Basque Country UPV/EHU, 01006 Vitoria-Gasteiz, Araba, Spain; (Y.V.); (G.P.); (J.L.P.); (J.Z.)
| | - Shifa Jebari-Benslaiman
- Biofisika Institute (UPV/EHU, CSIC), Department Biochemistry and Molecular Biology, University of the Basque Country University (UPV/EHU), 48940 Leioa, Bizkaia, Spain; (C.M.); (S.J.-B.)
| | - Marian M. de Pancorbo
- BIOMICs Research Group, Microfluidics Cluster UPV/EHU, Lascaray Research Center, University of the Basque Country UPV/EHU, 01009 Vitoria-Gasteiz, Araba, Spain; (M.R.); (M.M.d.P.)
| | - Jon Zarate
- NanoBioCel Research Group, Laboratory of Pharmacy and Pharmaceutical Technology, Faculty of Pharmacy, University of the Basque Country UPV/EHU, 01006 Vitoria-Gasteiz, Araba, Spain; (Y.V.); (G.P.); (J.L.P.); (J.Z.)
| | - Guiomar Perez de Nanclares
- Rare Diseases Research Group, Molecular (Epi) Genetics Laboratory, BioAraba Health Research Institute, Araba University Hospital-Txagorritxu, 01009 Vitoria-Gasteiz, Araba, Spain
- Correspondence: ; Tel.: +34-945007097
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22
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Luo S, Shao L, Geng R, Liu Q, Jiang W, Gong M, Zhang Y, He Y. Identification and biological characteristics of clear cell renal cell carcinoma associated urine-derived stem cells. Am J Transl Res 2021; 13:2143-2162. [PMID: 34017380 PMCID: PMC8129396] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2020] [Accepted: 01/12/2021] [Indexed: 06/12/2023]
Abstract
Urine-derived stem cells (USC) are isolated from voided urine and have demonstrated potential for use in tissue engineering and regenerative medicine therapies. Clear cell renal cell carcinoma (ccRCC) is a common urological malignancy that originates in the kidney. Since USC also originate in the kidney, the objective of this study was to investigate any biological differences between USC isolated from healthy patients and those isolated from ccRCC patients (rc-USC). We found that USC can be isolated from the voided urine of ccRCC patients (rc-USC) and have a morphology and function similar to those isolated from healthy donors. However, the rc-USC showed greater proliferation and invasion capacity than USC, and possessed some features of cancer cells; but the rc-UC were not able to form xenografts when implanted in vivo. We further performed RNA sequencing of rc-USC and USC and found several differentially expressed lncRNAs and mRNAs; however subsequent GO and KEGG enrichment analysis showed few pathway differences between these cells. Bioinformatic analyses and RT-PCR showed the expression of several known ccRCC-related genes in rc-USC expressed, as compared to USC derived from healthy donors. This study demonstrates that rc-USC displayed several cellular and genetic features of ccRCC cells, which suggests that this population of cells could provide a non-invasive approach for for the diagnosis, predication, disease modeling and therapeutic strategies targeting ccRCC.
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Affiliation(s)
- Shengjun Luo
- Department of Urology, The First Affiliated Hospital of Chongqing Medical UniversityChongqing, China
| | - Lan Shao
- Department of Rehabilitation, The First Affiliated Hospital of Chongqing Medical UniversityChongqing, China
| | - Ruizhi Geng
- Department of Urology, University of Tübingen HospitalTübingen, Germany
| | - Qingyuan Liu
- Department of Urology, The First Affiliated Hospital of Chongqing Medical UniversityChongqing, China
| | - Wencheng Jiang
- Department of Urology, The First Affiliated Hospital of Chongqing Medical UniversityChongqing, China
| | - Mengjia Gong
- Pediatric Research Institute, Children’s Hospital of Chongqing Medical UniversityChongqing, China
| | - Yuanyuan Zhang
- Wake Forest Institute of Regenerative Medicine, Wake Forest UniversityWinston Salem, NC, USA
| | - Yunfeng He
- Department of Urology, The First Affiliated Hospital of Chongqing Medical UniversityChongqing, China
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23
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Sun Y, Wang Y, Li Z, Guo Z. Isolation and Multiple Differentiation of Rat Pericardial Fluid Cells. Front Cell Dev Biol 2021; 9:614826. [PMID: 33644050 PMCID: PMC7905039 DOI: 10.3389/fcell.2021.614826] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/07/2020] [Accepted: 01/21/2021] [Indexed: 12/11/2022] Open
Abstract
Objective The aim of the present study is to isolate and analyze the characterization of pericardial fluid cells (PFCs) from rat and provides a morphological basis for the basic research and clinical application of PFCs. Methods After aseptic thoracotomy was performed, normal saline was injected into the pericardial cavity of 50 adult Sprague–Dawley rats. The mixture of diluted pericardial fluid was extracted, centrifuged, and cultured. The cell morphology of different generations in the pericardial fluid was observed on an inverted microscope. The expression levels of CD44, CD29, CD90, and pan-hematopoietic marker CD45 were analyzed via flow cytometry. The third-generation cells were used for osteogenic, adipogenic, and cardiac differentiation. Results PFCs were successfully isolated and subcultured. PFCs were predominantly circular in shape after 24 h of culture. Following subculture for 3 days, the cells demonstrated a spindle shape. The rat pericardial fluid contains cell populations with uniform morphology, good growth state, and strong proliferation ability. Flow cytometry results showed that CD29 (100%) and CD90 (99.3%) were positively expressed, whereas CD45 (0.30%) and CD44 (0.48%) were negatively expressed. The PFCs could differentiate into osteoblasts and adipocytes after being induced. Cardiac differentiation was also confirmed by cardiac troponin T (cTnT) and α-sarcomeric actin (α-SA) staining. Conclusion This study revealed that a subpopulation of cells was isolated from pericardial fluid, which exhibited progenitor cell features and multiple differentiation potency. PFCs could serve as an alternative cell source for myocardial tissue repair, engineering, and reconstruction.
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Affiliation(s)
- Ying Sun
- Henan Key Laboratory of Medical Tissue Regeneration, Xinxiang Medical University, Xinxiang, China.,Department of Cardiology, Zhengzhou Seventh People's Hospital, Zhengzhou, China
| | - Yan Wang
- Department of Cardiology, Zhengzhou Seventh People's Hospital, Zhengzhou, China
| | - Zongjin Li
- Henan Key Laboratory of Medical Tissue Regeneration, Xinxiang Medical University, Xinxiang, China
| | - Zhikun Guo
- Henan Key Laboratory of Medical Tissue Regeneration, Xinxiang Medical University, Xinxiang, China.,Department of Cardiology, Zhengzhou Seventh People's Hospital, Zhengzhou, China
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Zhang Y, Wang J, Yang B, Qiao R, Li A, Guo H, Ding J, Li H, Ye H, Wu D, Cui L, Yang S. Transfer of MicroRNA-216a-5p From Exosomes Secreted by Human Urine-Derived Stem Cells Reduces Renal Ischemia/Reperfusion Injury. Front Cell Dev Biol 2020; 8:610587. [PMID: 33415108 PMCID: PMC7783217 DOI: 10.3389/fcell.2020.610587] [Citation(s) in RCA: 26] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2020] [Accepted: 11/23/2020] [Indexed: 12/19/2022] Open
Abstract
Human urine-derived stem cells (USCs) protect rats against kidney ischemia/reperfusion (I/R) injury. Here we investigated the role of USCs exosomes (USCs-Exos) in protecting tubular endothelial cells and miRNA transfer in the kidney. Human USCs and USCs-Exos were isolated and verified by morphology and specific biomarkers. USC-Exos played a protective role in human proximal tubular epithelial cells (HK-2) exposed to hypoxia/reoxygenation (H/R). USCs-Exos were rich in miR-216a-5p, which targeted phosphatase and tensin homolog (PTEN) and regulated cell apoptosis through the Akt pathway. In HK-2 cells exposed to H/R, incubation with USC-Exos increased miR-216-5p, decreased PTEN levels, and stimulated Akt phosphorylation. Exposure of hypoxic HK-2 cells to USCs-Exos pretreated with anti-miR-216a-5p can prevent the increase of miR-216-5p and Akt phosphorylation levels, restore PTEN expression, and promote apoptosis. The dual-luciferase reported gene assay in HK-2 cells confirmed that miR-216a-5p targeted PTEN. In rats with I/R injury, intravenous infusion of USCs-Exos can effectively induce apoptosis suppression and functional protection, which is associated with decreased PTEN. Infusion of exosomes from anti-miR-216a-5p-transfected USCs weakened the protective effect in the I/R model. Therefore, USCs-Exos can reduce renal I/R injury by transferring miR-216a-5p targeting PTEN. Potentially, USCs-Exos rich in miR-216a-5p can serve as a promising therapeutic option for AKI.
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Affiliation(s)
- Yinmei Zhang
- Department of Laboratory Medicine, Peking University Third Hospital, Beijing, China
| | - Junxiong Wang
- Department of Gastroenterology, Beijing Friendship Hospital, Capital Medical University, Beijing, China
| | - Boxin Yang
- Department of Laboratory Medicine, Peking University Third Hospital, Beijing, China
| | - Rui Qiao
- Department of Laboratory Medicine, Peking University Third Hospital, Beijing, China
| | - Aiwei Li
- Department of Laboratory Medicine, Peking University Third Hospital, Beijing, China
| | - Han Guo
- Department of Laboratory Medicine, Peking University Third Hospital, Beijing, China
| | - Jie Ding
- Department of Laboratory Medicine, Peking University Third Hospital, Beijing, China
| | - Hui Li
- Department of Laboratory Medicine, Peking University Third Hospital, Beijing, China
| | - Hong Ye
- Department of Laboratory Medicine, Peking University Third Hospital, Beijing, China
| | - Di Wu
- Department of Laboratory Medicine, Peking University Third Hospital, Beijing, China
| | - Liyan Cui
- Department of Laboratory Medicine, Peking University Third Hospital, Beijing, China
| | - Shuo Yang
- Department of Laboratory Medicine, Peking University Third Hospital, Beijing, China
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Exosomes Derived from Human Urine-Derived Stem Cells Inhibit Intervertebral Disc Degeneration by Ameliorating Endoplasmic Reticulum Stress. OXIDATIVE MEDICINE AND CELLULAR LONGEVITY 2020; 2020:6697577. [PMID: 33488928 PMCID: PMC7787770 DOI: 10.1155/2020/6697577] [Citation(s) in RCA: 43] [Impact Index Per Article: 8.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/09/2020] [Revised: 11/14/2020] [Accepted: 11/18/2020] [Indexed: 12/12/2022]
Abstract
Objective This study is aimed at determining the effects of human urine-derived stem cell-derived exosomes (USCs-exos) on pressure-induced nucleus pulposus cell (NPC) apoptosis and intervertebral disc degeneration (IDD) and on the ERK and AKT signaling pathways. Methods The NPCs were obtained from patients with herniated lumbar discs. Western blot analysis (WB) and quantitative real-time polymerase chain reaction (qRT-PCR) were used to determine endoplasmic reticulum (ER) stress levels of NPCs under stress. Human USCs were identified using an inverted microscope, three-line differentiation experiments, and flow cytometry. A transmission microscope, nanoparticle size analysis, and WB procedures were used to identify the extracted exosomes and observe NPC uptake. A control group, a 48 h group, and a USCs-exos group were established. The control group was untreated, and the 48 h group was pressure-trained for 48 h, while the USCs-exos group was pressure-trained for 48 h and treated with USCs-exos. WB, qRT-PCR, and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) analysis were used to determine the ER stress levels in stress conditions and after exosomal treatment. The AKT and ERK pathways were partially detected. Magnetic Resonance Imaging (MRI) and computed tomography (CT) were used to evaluate cell degeneration while exosomal effects on the intervertebral disc (IVD) tissue were determined by hematoxylin and eosin (HE) staining, Safranin O-fast green staining, immunohistochemical staining (IHC), nuclear magnetic resonance (NMR), spectrometric detection, and total correlation spectroscopy (TOCSY). IVD metabolites were also identified and quantified. Results After pressure culture, ER stress markers (GRP78 and C/EBP homologous protein (CHOP)) in the NPCs were significantly elevated with time (p < 0.05). Human USCs are short and spindle-shaped. They can successfully undergo osteogenic, adipogenic, and chondrogenic differentiation. In this study, these stem cells were found to be positive for CD29, CD44, and CD73. The exosomes were centrally located with a diameter of 50-100 nm. CD63 and Tsg101 were highly expressed while the expression of Calnexin was suppressed. The exosomes can be ingested by NPCs. USCs-exos significantly improved ER stress responses and inhibited excessive activation of the unfolded protein response (UPR) as well as cell apoptosis and disc degeneration through the AKT and ERK signaling pathways (p < 0.05). Conclusion Through the AKT and ERK signaling pathways, USCs-exos significantly inhibit ER stress-induced cell apoptosis and IDD under pressure conditions. It is, therefore, a viable therapeutic strategy.
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Chen Y, Xu Y, Li M, Shi Q, Chen C. Application of Autogenous Urine-Derived Stem Cell Sheet Enhances Rotator Cuff Healing in a Canine Model. Am J Sports Med 2020; 48:3454-3466. [PMID: 33136424 DOI: 10.1177/0363546520962774] [Citation(s) in RCA: 21] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
BACKGROUND A repaired rotator cuff (RC) often heals with interposed scar tissue, making repairs prone to failure. Urine-derived stem cells (USCs), with robust proliferation ability and multilineage differentiation, can be isolated from urine, avoiding invasive and painful surgical procedures for harvesting the cells. These advantages make it a novel cell source for autologous transplantation to enhance RC healing. HYPOTHESIS Implantation of an autogenous USC sheet to the injury site will enhance RC healing. STUDY DESIGN Controlled laboratory study. METHODS USCs isolated from urine were cultured using ascorbic acid and transforming growth factor β3 to form a cell sheet. Sixteen male mature beagles underwent bilateral shoulder surgery. The right shoulder underwent infraspinatus tendon (IT) insertion detachment and repair only, and the other was subjected to IT insertion detachment and repair, followed by autogenous USC sheet implantation. Among the animals, 3 received a Dil (1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate)- labeled USC sheet implant in the right shoulder and were sacrificed at postoperative 6 weeks for cell tracking. The other animals were sacrificed at postoperative 12 weeks, and the IT-humerus complexes were harvested for gross observation, micro-computed tomography evaluation and histological analysis (n = 5), and mechanical testing (n = 8). Additionally, 13 unpaired canine cadaveric shoulders were included as native controls. RESULTS Micro-computed tomography analysis showed that the USC sheet group had a significant increase in bone volume/total volume and trabecular thickness at the RC healing site when compared with the control group (P < .05 for all). Histologically, the Dil-labeled USC sheet was still visible at the RC healing site, which suggested that the implanted USCs remained viable at postoperative 6 weeks. Meanwhile, the healing interface in the USC sheet group regenerated significantly more enthesis-like tissue than did that of the control group (P < .05). Additionally, the healing interface in the USC sheet group presented a larger fibrocartilage area, more proteoglycan deposition, and higher collagen birefringence than did that of the control group (P < .05 for all). Biomechanically, the USC sheet group showed significantly higher failure load and stiffness versus the control group (P < .05 for all). CONCLUSION A USC sheet was able to enhance RC healing in a canine model. CLINICAL RELEVANCE The findings of the study showed that USC sheet implantation could serve as a practical application for RC healing.
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Affiliation(s)
- Yang Chen
- Department of Sport Medicine, Xiangya Hospital, Central South University, Changsha, China
| | - Yan Xu
- Department of Sport Medicine, Xiangya Hospital, Central South University, Changsha, China
| | - Muzhi Li
- Department of Sport Medicine, Xiangya Hospital, Central South University, Changsha, China
| | - Qiang Shi
- Department of Sport Medicine, Xiangya Hospital, Central South University, Changsha, China
| | - Can Chen
- Department of Orthopedics, Xiangya Hospital, Central South University, Changsha, China
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Zhao G, Ge Y, Zhang C, Zhang L, Xu J, Qi L, Li W. Progress of Mesenchymal Stem Cell-Derived Exosomes in Tissue Repair. Curr Pharm Des 2020; 26:2022-2037. [PMID: 32310043 DOI: 10.2174/1381612826666200420144805] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2019] [Accepted: 03/25/2020] [Indexed: 12/17/2022]
Abstract
Mesenchymal stem cells (MSCs) are a kind of adult stem cells with self-replication and multidirectional differentiation, which can differentiate into tissue-specific cells under physiological conditions, maintaining tissue self-renewal and physiological functions. They play a role in the pathological condition by lateral differentiation into tissue-specific cells, replacing damaged tissue cells by playing the role of a regenerative medicine , or repairing damaged tissues through angiogenesis, thereby, regulating immune responses, inflammatory responses, and inhibiting apoptosis. It has become an important seed cell for tissue repair and organ reconstruction, and cell therapy based on MSCs has been widely used clinically. The study found that the probability of stem cells migrating to the damaged area after transplantation or differentiating into damaged cells is very low, so the researchers believe the leading role of stem cell transplantation for tissue repair is paracrine secretion, secreting growth factors, cytokines or other components. Exosomes are biologically active small vesicles secreted by MSCs. Recent studies have shown that they can transfer functional proteins, RNA, microRNAs, and lncRNAs between cells, and greatly reduce the immune response. Under the premise of promoting proliferation and inhibition of apoptosis, they play a repair role in tissue damage, which is caused by a variety of diseases. In this paper, the biological characteristics of exosomes (MSCs-exosomes) derived from mesenchymal stem cells, intercellular transport mechanisms, and their research progress in the field of stem cell therapy are reviewed.
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Affiliation(s)
- Guifang Zhao
- School of Basic Medical Sciences, Jilin Medical University, Jilin 132013, China.,Qingyuan People's Hospital, The Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan 511518, Guangzhou Province, China
| | - Yiwen Ge
- School of Basic Medical Sciences, Jilin Medical University, Jilin 132013, China
| | - Chenyingnan Zhang
- School of Basic Medical Sciences, Jilin Medical University, Jilin 132013, China
| | - Leyi Zhang
- School of Pharmacy, Jilin Medical University, Jilin 132013, China
| | - Junjie Xu
- School of Basic Medical Sciences, Jilin Medical University, Jilin 132013, China
| | - Ling Qi
- Qingyuan People's Hospital, The Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan 511518, Guangzhou Province, China.,School of Basic Medical Sciences, Department of Pathophysiology, Jilin Medical University, Jilin 132013, China
| | - Wenliang Li
- School of Pharmacy, Jilin Medical University, Jilin 132013, China
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28
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Li X, Liao J, Su X, Li W, Bi Z, Wang J, Su Q, Huang H, Wei Y, Gao Y, Li J, Liu L, Wang C. Human urine-derived stem cells protect against renal ischemia/reperfusion injury in a rat model via exosomal miR-146a-5p which targets IRAK1. Theranostics 2020; 10:9561-9578. [PMID: 32863945 PMCID: PMC7449916 DOI: 10.7150/thno.42153] [Citation(s) in RCA: 118] [Impact Index Per Article: 23.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/16/2019] [Accepted: 07/16/2020] [Indexed: 02/06/2023] Open
Abstract
Rationale: Ischemia/reperfusion injury (IRI) is a major cause of acute kidney injury (AKI) that is associated with high morbidity and mortality, and for which specific treatments are lacking. In this study, we investigated the protective effect of human urine-derived stem cells (USCs) and their exosomes against IRI-induced AKI to explore the potential of these cells as a new therapeutic strategy. Methods: USCs were derived from fresh human urine. Cell surface marker expression was analyzed by flow cytometry to determine the characteristics of the stem cells. Adult male Sprague-Dawley rats were used to generate a lethal renal IRI model. One dose of USCs (2×106 cells/ml) or exosomes (20 µg/1 ml) in the experimental groups or saline (1 ml) in the control group was administered intravenously immediately after blood reperfusion. Blood was drawn every other day for measurement of serum creatinine (sCr) and blood urea nitrogen (BUN) levels. The kidneys were harvested for RNA and protein extraction to examine the levels of apoptosis and tubule injury. In vitro, the hypoxia-reoxygenation (H/R) model in human kidney cortex/proximal tubule cells (HK2) was used to analyze the protective ability of USC-derived exosomes (USC-Exo). Quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR), western blotting, superoxide dismutase activity, and malonaldehyde content analyses were used to evaluate oxidative stress in HK2 cells treated with USC-Exo after H/R. Exosomal microRNA sequencing techniques and bioinformatics analysis were used to search for enriched miRNAs in the exosomes and interacting genes. The interaction between miRNAs and the 3' untranslated region of the target gene was detected using a dual luciferase reporting system. The miRNA mimic and inhibitor were used to regulate the miRNA level in HK2 cells. Results: Treatment with USCs led to reductions in the levels of sCr, BUN, and renal tubular cell apoptosis; inhibited the infiltration of inflammatory cells; and protected renal function in the rat IRI model. Additionally, USC-derived exosomes protected against IRI-induced renal damage. miR-146a-5p was the most abundant miRNA in exosomes obtained from the conditioned medium (CM) of USCs. miR-146a-5p targeted and degraded the 3'UTR of interleukin-1 receptor-associated kinase 1 (IRAK1) mRNA, subsequently inhibited the activation of nuclear factor (NF)-κB signaling, and protected HK2 cells from H/R injury. USC transplantation also upregulated miR-146a-5p expression, downregulated IRAK1 expression and inhibited nuclear translocation of NF-κB p65 in the kidney of the rat IRI model. Conclusions: According to our experimental results, USCs could protect against renal IRI via exosomal miR-146a-5p, which could target the 3'UTR of IRAK1 and subsequently inhibit the activation of NF-κB signaling and infiltration of inflammatory cells to protect renal function. As a novel cell source, USCs represent a promising non-invasive approach for the treatment of IRI.
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Urine-Derived Induced Pluripotent Stem Cells in Cardiovascular Disease. Cardiol Res Pract 2020; 2020:3563519. [PMID: 32377426 PMCID: PMC7199581 DOI: 10.1155/2020/3563519] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/20/2019] [Revised: 11/26/2019] [Accepted: 12/17/2019] [Indexed: 12/28/2022] Open
Abstract
Recent studies have demonstrated that stem cells are equipped with the potential to differentiate into various types of cells, including cardiomyocytes. Meanwhile, stem cells are highly promising in curing cardiovascular diseases. However, owing to the ethical challenges posed in stem cell acquisition and the complexity and invasive nature of the method, large-scale expansions and clinical applications in the laboratory have been limited. The current generation of cardiomyocytes is available from diverse sources; urine is one of the promising sources among them. Although advanced research was established in the generation of human urine cells as cardiomyocytes, the reprogramming of urine cells to cardiomyocytes remains unclear. In this context, it is necessary to develop a minimally invasive method to create induced pluripotent stem cells (iPSCs). This review focuses on the latest advances in research on urine-derived iPSCs and their application mechanisms in cardiovascular diseases.
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Zheng J, Yun W, Park J, Kang PJ, Lee G, Song G, Kim IY, You S. Long-term expansion of directly reprogrammed keratinocyte-like cells and in vitro reconstitution of human skin. J Biomed Sci 2020; 27:56. [PMID: 32312260 PMCID: PMC7171822 DOI: 10.1186/s12929-020-00642-1] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2019] [Accepted: 03/26/2020] [Indexed: 11/29/2022] Open
Abstract
Background Human keratinocytes and derived products are crucial for skin repair and regeneration. Despite substantial advances in engineered skin equivalents, their poor availability and immunorejection remain major challenges in skin grafting. Methods Induced keratinocyte-like cells (iKCs) were directly reprogrammed from human urine cells by retroviral transduction of two lineage-specific transcription factors BMI1 and △NP63α (BN). Expression of keratinocyte stem cell or their differentiation markers were assessed by PCR, immunofluorescence and RNA-Sequencing. Regeneration capacity of iKCs were assessed by reconstitution of a human skin equivalent under air-interface condition. Results BN-driven iKCs were similar to primary keratinocytes (pKCs) in terms of their morphology, protein expression, differentiation potential, and global gene expression. Moreover, BN-iKCs self-assembled to form stratified skin equivalents in vitro. Conclusions This study demonstrated an approach to generate human iKCs that could be directly reprogrammed from human somatic cells and extensively expanded in serum- and feeder cell-free systems, which will facilitate their broad applicability in an efficient and patient-specific manner.
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Affiliation(s)
- Jie Zheng
- Laboratory of Cell Function Regulation, Department of Biotechnology, College of Life Sciences and Biotechnology, Korea University, Seoul, 02841, Republic of Korea.,Institute of Animal Molecular Biotechnology, College of Life Sciences and Biotechnology, Korea University, Seoul, 02841, Republic of Korea
| | - Wonjin Yun
- Laboratory of Cell Function Regulation, Department of Biotechnology, College of Life Sciences and Biotechnology, Korea University, Seoul, 02841, Republic of Korea.,Institute of Animal Molecular Biotechnology, College of Life Sciences and Biotechnology, Korea University, Seoul, 02841, Republic of Korea
| | - Junghyun Park
- Laboratory of Cell Function Regulation, Department of Biotechnology, College of Life Sciences and Biotechnology, Korea University, Seoul, 02841, Republic of Korea.,Institute of Animal Molecular Biotechnology, College of Life Sciences and Biotechnology, Korea University, Seoul, 02841, Republic of Korea
| | - Phil Jun Kang
- Laboratory of Cell Function Regulation, Department of Biotechnology, College of Life Sciences and Biotechnology, Korea University, Seoul, 02841, Republic of Korea.,Institute of Animal Molecular Biotechnology, College of Life Sciences and Biotechnology, Korea University, Seoul, 02841, Republic of Korea
| | - Gilju Lee
- Department of Pathology, College of Medicine, Korea University Guro Hospital, Seoul, 08308, Republic of Korea
| | - Gwonhwa Song
- Institute of Animal Molecular Biotechnology, College of Life Sciences and Biotechnology, Korea University, Seoul, 02841, Republic of Korea.
| | - In Yong Kim
- Laboratory of Cell Function Regulation, Department of Biotechnology, College of Life Sciences and Biotechnology, Korea University, Seoul, 02841, Republic of Korea.
| | - Seungkwon You
- Laboratory of Cell Function Regulation, Department of Biotechnology, College of Life Sciences and Biotechnology, Korea University, Seoul, 02841, Republic of Korea. .,Institute of Animal Molecular Biotechnology, College of Life Sciences and Biotechnology, Korea University, Seoul, 02841, Republic of Korea.
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31
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Urine-Derived Stem Cells: Applications in Regenerative and Predictive Medicine. Cells 2020; 9:cells9030573. [PMID: 32121221 PMCID: PMC7140531 DOI: 10.3390/cells9030573] [Citation(s) in RCA: 37] [Impact Index Per Article: 7.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/17/2019] [Revised: 02/17/2020] [Accepted: 02/25/2020] [Indexed: 12/14/2022] Open
Abstract
Despite being a biological waste, human urine contains a small population of cells with self-renewal capacity and differentiation potential into several cell types. Being derived from the convoluted tubules of nephron, renal pelvis, ureters, bladder and urethra, urine-derived stem cells (UDSC) have a similar phenotype to mesenchymal stroma cells (MSC) and can be reprogrammed into iPSC (induced pluripotent stem cells). Having simple, safer, low-cost and noninvasive collection procedures, the interest in UDSC has been growing in the last decade. With great potential in regenerative medicine applications, UDSC can also be used as biological models for pharmacology and toxicology tests. This review describes UDSC biological characteristics and differentiation potential and their possible use, including the potential of UDSC-derived iPSC to be used in drug discovery and toxicology, as well as in regenerative medicine. Being a new cellular platform amenable to noninvasive collection for disease stratification and personalized therapy could be a future application for UDSC.
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32
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Abbas TO, Ali TA, Uddin S. Urine as a Main Effector in Urological Tissue Engineering-A Double-Edged Sword. Cells 2020; 9:cells9030538. [PMID: 32110928 PMCID: PMC7140397 DOI: 10.3390/cells9030538] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2019] [Revised: 01/28/2020] [Accepted: 01/29/2020] [Indexed: 12/15/2022] Open
Abstract
In order to reconstruct injured urinary tract tissues, biodegradable scaffolds with autologous seeded cells are explored in this work. However, when cells are obtained via biopsy from individuals who have damaged organs due to infection, congenital disorders, or cancer, this can result in unhealthy engineered cells and donor site morbidity. Thus, neo-organ construction through an alternative cell source might be useful. Significant advancements in the isolation and utilization of urine-derived stem cells have provided opportunities for this less invasive, limitless, and versatile source of cells to be employed in urologic tissue-engineered replacement. These cells have a high potential to differentiate into urothelial and smooth muscle cells. However, urinary tract reconstruction via tissue engineering is peculiar as it takes place in a milieu of urine that imposes certain risks on the implanted cells and scaffolds as a result of the highly cytotoxic nature of urine and its detrimental effect on both growth and differentiation of these cells. Both of these projections should be tackled thoughtfully when designing a suitable approach for repairing urinary tract defects and applying the needful precautions is vital.
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Affiliation(s)
- Tariq O. Abbas
- Laboratory for Stem Cell Research, Department of Health Science and Technology, Aalborg University, 9220 Aalborg, Denmark
- Pediatric Urology Section, Sidra Medicine, Doha 26999, Qatar
- College of Medicine, Qatar University, Doha 2713, Qatar
- Surgery Department, Weill Cornell Medicine—Qatar, Doha 24144, Qatar
- Correspondence: or ; Tel.: +974-550-93-651
| | - Tayyiba A. Ali
- Translational Research Institute, Academic Health System, Hamad Medical Corporation, Doha 3050, Qatar; (T.A.A.); (S.U.)
| | - Shahab Uddin
- Translational Research Institute, Academic Health System, Hamad Medical Corporation, Doha 3050, Qatar; (T.A.A.); (S.U.)
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33
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Xu Y, Zhang T, Chen Y, Shi Q, Li M, Qin T, Hu J, Lu H, Liu J, Chen C. Isolation and Characterization of Multipotent Canine Urine-Derived Stem Cells. Stem Cells Int 2020; 2020:8894449. [PMID: 33061993 PMCID: PMC7545436 DOI: 10.1155/2020/8894449] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2020] [Revised: 08/20/2020] [Accepted: 08/28/2020] [Indexed: 12/11/2022] Open
Abstract
Current cell-based therapies on musculoskeletal tissue regeneration were mostly determined in rodent models. However, a direct translation of those promising cell-based therapies to humans exists a significant hurdle. For solving this problem, canine has been developed as a new large animal model to bridge the gap from rodents to humans. In this study, we reported the isolation and characterization of urine-derived stem cells (USCs) from mature healthy beagle dogs. The isolated cells showed fibroblast-like morphology and had good clonogenicity and proliferation. Meanwhile, these cells positively expressed multiple markers of MSCs (CD29, CD44, CD90, and CD73), but negatively expressed for hematopoietic antigens (CD11b, CD34, and CD45). Additionally, after induction culturing, the isolated cells can be differentiated into osteogenic, adipogenic, chondrogenic, and tenogenic lineages. The successful isolation and verification of USCs from canine were useful for studying cell-based therapies and developing new treatments for musculoskeletal injuries using the preclinical canine model.
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Affiliation(s)
- Yan Xu
- 1Key Laboratory of Organ Injury, Aging and Regenerative Medicine of Hunan Province, Changsha, China 410008
- 2Hunan Engineering Research Center of Sports and Health, Changsha, China 410008
- 3Xiangya Hospital-International Chinese Musculoskeletal Research Society Sports Medicine Research Centre, Changsha, China 410008
- 4Department of Sports Medicine, Xiangya Hospital, Central South University, Changsha, China 410008
| | - Tao Zhang
- 1Key Laboratory of Organ Injury, Aging and Regenerative Medicine of Hunan Province, Changsha, China 410008
- 2Hunan Engineering Research Center of Sports and Health, Changsha, China 410008
- 3Xiangya Hospital-International Chinese Musculoskeletal Research Society Sports Medicine Research Centre, Changsha, China 410008
- 4Department of Sports Medicine, Xiangya Hospital, Central South University, Changsha, China 410008
| | - Yang Chen
- 1Key Laboratory of Organ Injury, Aging and Regenerative Medicine of Hunan Province, Changsha, China 410008
- 2Hunan Engineering Research Center of Sports and Health, Changsha, China 410008
- 3Xiangya Hospital-International Chinese Musculoskeletal Research Society Sports Medicine Research Centre, Changsha, China 410008
- 4Department of Sports Medicine, Xiangya Hospital, Central South University, Changsha, China 410008
| | - Qiang Shi
- 1Key Laboratory of Organ Injury, Aging and Regenerative Medicine of Hunan Province, Changsha, China 410008
- 2Hunan Engineering Research Center of Sports and Health, Changsha, China 410008
- 3Xiangya Hospital-International Chinese Musculoskeletal Research Society Sports Medicine Research Centre, Changsha, China 410008
- 4Department of Sports Medicine, Xiangya Hospital, Central South University, Changsha, China 410008
| | - Muzhi Li
- 1Key Laboratory of Organ Injury, Aging and Regenerative Medicine of Hunan Province, Changsha, China 410008
- 2Hunan Engineering Research Center of Sports and Health, Changsha, China 410008
- 3Xiangya Hospital-International Chinese Musculoskeletal Research Society Sports Medicine Research Centre, Changsha, China 410008
- 4Department of Sports Medicine, Xiangya Hospital, Central South University, Changsha, China 410008
| | - Tian Qin
- 1Key Laboratory of Organ Injury, Aging and Regenerative Medicine of Hunan Province, Changsha, China 410008
- 2Hunan Engineering Research Center of Sports and Health, Changsha, China 410008
- 3Xiangya Hospital-International Chinese Musculoskeletal Research Society Sports Medicine Research Centre, Changsha, China 410008
- 5Department of Spine Surgery, Xiangya Hospital, Central South University, Changsha, Hunan, China 410008
| | - Jianzhong Hu
- 1Key Laboratory of Organ Injury, Aging and Regenerative Medicine of Hunan Province, Changsha, China 410008
- 2Hunan Engineering Research Center of Sports and Health, Changsha, China 410008
- 3Xiangya Hospital-International Chinese Musculoskeletal Research Society Sports Medicine Research Centre, Changsha, China 410008
- 5Department of Spine Surgery, Xiangya Hospital, Central South University, Changsha, Hunan, China 410008
| | - Hongbin Lu
- 1Key Laboratory of Organ Injury, Aging and Regenerative Medicine of Hunan Province, Changsha, China 410008
- 2Hunan Engineering Research Center of Sports and Health, Changsha, China 410008
- 3Xiangya Hospital-International Chinese Musculoskeletal Research Society Sports Medicine Research Centre, Changsha, China 410008
- 4Department of Sports Medicine, Xiangya Hospital, Central South University, Changsha, China 410008
| | - Jun Liu
- 6Department of Limbs (Foot and Hand) Microsurgery, Affiliated Chenzhou No.1 People's Hospital, Southern Medical University, Chenzhou, China 423000
| | - Can Chen
- 1Key Laboratory of Organ Injury, Aging and Regenerative Medicine of Hunan Province, Changsha, China 410008
- 2Hunan Engineering Research Center of Sports and Health, Changsha, China 410008
- 3Xiangya Hospital-International Chinese Musculoskeletal Research Society Sports Medicine Research Centre, Changsha, China 410008
- 7Department of Orthopedics, Xiangya Hospital, Central South University, Changsha, China 410008
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Sato M, Takizawa H, Nakamura A, Turner BJ, Shabanpoor F, Aoki Y. Application of Urine-Derived Stem Cells to Cellular Modeling in Neuromuscular and Neurodegenerative Diseases. Front Mol Neurosci 2019; 12:297. [PMID: 31920531 PMCID: PMC6915080 DOI: 10.3389/fnmol.2019.00297] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2019] [Accepted: 11/20/2019] [Indexed: 12/11/2022] Open
Abstract
Neuromuscular and neurodegenerative diseases are mostly modeled using genetically modified animals such as mice. However, animal models do not recapitulate all the phenotypes that are specific to human disease. This is mainly due to the genetic, anatomical and physiological difference in the neuromuscular systems of animals and humans. The emergence of direct and indirect human somatic cell reprogramming technologies may overcome this limitation because they enable the use of disease and patient-specific cellular models as enhanced platforms for drug discovery and autologous cell-based therapy. Induced pluripotent stem cells (iPSCs) and urine-derived stem cells (USCs) are increasingly employed to recapitulate the pathophysiology of various human diseases. Recent cell-based modeling approaches utilize highly complex differentiation systems that faithfully mimic human tissue- and organ-level dysfunctions. In this review, we discuss promising cellular models, such as USC- and iPSC-based approaches, that are currently being used to model human neuromuscular and neurodegenerative diseases.
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Affiliation(s)
- Mitsuto Sato
- Department of Molecular Therapy, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Kodaira, Japan.,Department of Medicine (Neurology and Rheumatology), Shinshu University School of Medicine, Matsumoto, Japan
| | - Hotake Takizawa
- Department of Molecular Therapy, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Kodaira, Japan
| | - Akinori Nakamura
- Department of Clinical Research, National Hospital Organization Matsumoto Medical Center, Matsumoto, Japan
| | - Bradley J Turner
- The Florey Institute of Neuroscience and Mental Health, University of Melbourne, Parkville, VIC, Australia
| | - Fazel Shabanpoor
- The Florey Institute of Neuroscience and Mental Health, University of Melbourne, Parkville, VIC, Australia
| | - Yoshitsugu Aoki
- Department of Molecular Therapy, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Kodaira, Japan
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35
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Lin W, Xu L, Li G. A novel protocol for isolation and culture of multipotent progenitor cells from human urine. J Orthop Translat 2019; 19:12-17. [PMID: 31844609 PMCID: PMC6896728 DOI: 10.1016/j.jot.2019.02.005] [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] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/14/2018] [Revised: 02/10/2019] [Accepted: 02/22/2019] [Indexed: 12/13/2022] Open
Abstract
Cell therapy holds promise for treating a variety of diseases. Seeking available source of adult stem cells remains a great challenge in cell therapy. Urine is considered as an ideal source of adult stem cells which can be easily acquired by noninvasive methods. However, specific cell types in urine have not been well documented. Here, the aim of our study is to identify cell types in urine, and isolate and expand progenitor/stem cells from human urine and further evaluate their multipotency. Urine samples were collected from healthy donors. The cell suspension was seeded and selected because of plastic adherence. Colonies with two different morphologies appeared 7 days later. One type of colony was spindle-shaped and fibroblast-like; the other cell type displayed rounder shape. Cells that displayed fibroblast-like shape were selectively enriched using a cloning cylinder. Then multidifferentiation induction assays and immunophenotyping assays were applied. Characterization assays indicated that adherent cells possessed potent trilineage differentiation capacity and expressed CXCR4 and Nanog, as well as some mesenchymal stem cell surface antigens (including CD90 and CD44). Taken together, at least two cell populations exist in human urine. A stem cell subpopulation with trilineage differentiation capacity from human urine can be selectively enriched using the cloning cylinder method. Urine may become an ideal source of adult stem cells for cell therapy and further clinical implications.
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Affiliation(s)
- Weiping Lin
- Department of Orthopaedics & Traumatology, Faculty of Medicine, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong, PR China
- Stem Cells and Regenerative Medicine Laboratory, Lui Che Woo Institute of Innovative Medicine, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong, PR China
| | - Liangliang Xu
- Key Laboratory of Orthopaedics & Traumatology, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, The First Clinical Medical College, Guangzhou University of Chinese Medicine, Guangzhou, PR China
| | - Gang Li
- Department of Orthopaedics & Traumatology, Faculty of Medicine, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong, PR China
- Stem Cells and Regenerative Medicine Laboratory, Lui Che Woo Institute of Innovative Medicine, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong, PR China
- The CUHK-ACC Space Medicine Centre on Health Maintenance of Musculoskeletal System, The Chinese University of Hong Kong Shenzhen Research Institute, Shenzhen, PR China
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36
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Falzarano MS, Ferlini A. Urinary Stem Cells as Tools to Study Genetic Disease: Overview of the Literature. J Clin Med 2019; 8:jcm8050627. [PMID: 31071994 PMCID: PMC6572423 DOI: 10.3390/jcm8050627] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2019] [Revised: 05/03/2019] [Accepted: 05/06/2019] [Indexed: 02/07/2023] Open
Abstract
Urine specimens represent a novel and non-invasive approach to isolate patient-specific stem cells by easy and low-cost procedures, replacing the traditional sources (muscle/skin biopsy/adipose tissue) obtained with invasive and time-consuming methods. Urine-derived stem cells (USCs) can be used in a broad field of applications, such as regenerative medicine, cell therapy, diagnostic testing, disease modelling and drug screening. USCs are a good source of cells for generating induced pluripotent stem cells (iPSCs) and importantly, they can also be directly converted into specific cell lines. In this review, we show the features of USCs and their use as a promising in vitro model to study genetic diseases.
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Affiliation(s)
- Maria Sofia Falzarano
- UOL (Unita` Operativa Logistica) of Medical Genetics, University of Ferrara, 44121 Ferrara, Italy.
| | - Alessandra Ferlini
- UOL (Unita` Operativa Logistica) of Medical Genetics, University of Ferrara, 44121 Ferrara, Italy.
- Neuromuscular Unit, Great Ormond Street Hospital, University College London, Bloomsbury, London WC1E 6BT, UK.
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37
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Pavathuparambil Abdul Manaph N, Al-Hawaas M, Bobrovskaya L, Coates PT, Zhou XF. Urine-derived cells for human cell therapy. Stem Cell Res Ther 2018; 9:189. [PMID: 29996911 PMCID: PMC6042455 DOI: 10.1186/s13287-018-0932-z] [Citation(s) in RCA: 54] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022] Open
Abstract
Desirable cells for human cell therapy would be ones that can be generated by simple isolation and culture techniques using a donor sample obtained by non-invasive methods. To date, the different donor-specific cells that can be isolated from blood, skin, and hair require invasive methods for sample isolation and incorporate complex and costly reagents to culture. These cells also take considerable time for their in-vitro isolation and expansion. Previous studies suggest that donor-derived cells, namely urine stem cells and renal cells, may be isolated from human urine samples using a cost-effective and simple method of isolation, incorporating not such complex reagents. Moreover, the isolated cells, particularly urine stem cells, are superior to conventional stem cell sources in terms of favourable gene profile and inherent multipotent potential. Transdifferentiation or differentiation of human urine-derived cells can generate desirable cells for regenerative therapy. In this review, we intended to discuss the characteristics and therapeutic applications of urine-derived cells for human cell therapy. Conclusively, with detailed study and optimisation, urine-derived cells have a prospective future to generate functional lineage-specific cells for patients from a clinical translation point of view.
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Affiliation(s)
- Nimshitha Pavathuparambil Abdul Manaph
- Central Northern Adelaide Renal and Transplantation Service, Royal Adelaide Hospital, Adelaide, 5000 South Australia
- School of Pharmacy and Medical Sciences, Sansom Institute, University of South Australia, Adelaide, 5000 South Australia
- School of Medicine, Faculty of Health Sciences, University of Adelaide, Adelaide, 5000 South Australia
| | - Mohammed Al-Hawaas
- School of Pharmacy and Medical Sciences, Sansom Institute, University of South Australia, Adelaide, 5000 South Australia
| | - Larisa Bobrovskaya
- School of Pharmacy and Medical Sciences, Sansom Institute, University of South Australia, Adelaide, 5000 South Australia
| | - Patrick T. Coates
- Central Northern Adelaide Renal and Transplantation Service, Royal Adelaide Hospital, Adelaide, 5000 South Australia
- School of Medicine, Faculty of Health Sciences, University of Adelaide, Adelaide, 5000 South Australia
| | - Xin-Fu Zhou
- School of Pharmacy and Medical Sciences, Sansom Institute, University of South Australia, Adelaide, 5000 South Australia
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