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Li X, Luo X, Zhang X, Guo Y, Cheng L, Cheng M, Tang S, Gong Y. COL1A1 promotes cell proliferation, cell cycle progression, and anoikis resistance in granulosa cells of chicken pre-ovulatory follicles. Int J Biol Macromol 2025; 306:141524. [PMID: 40020834 DOI: 10.1016/j.ijbiomac.2025.141524] [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: 07/02/2024] [Revised: 02/25/2025] [Accepted: 02/25/2025] [Indexed: 03/03/2025]
Abstract
Chicken follicular granulosa cells (GCs) are the earliest differentiated follicular somatic cells, which play a crucial role throughout follicular growth and development. The extracellular matrix (ECM) plays a key role in maintaining cell-cell interactions and communication during follicular development. This study investigated the effects of the COL1A1 gene, a major component of ECM, on chicken pre-ovulatory follicular granulosa cells (PO-GCs) and the related regulatory mechanism. Transcriptomic analysis results showed that silencing COL1A1 significantly inhibited GCs proliferation, cell cycle, and anoikis-related biological functions and pathways. The overexpression of endogenous COL1A1 promoted the GCs proliferation through the ERK1/2 signaling pathway, increased the number of GCs in the S/G2 phase of the cell cycle, and enhanced anoikis resistance of GCs. The exogenous addition of collagen Ι (Col Ι) promoted GCs proliferation but did not affect the cell cycle progression and anoikis resistance of GCs. In addition, we identified multiple genes involved in COL1A1 knockdown-induced anoikis in GCs, of which 7 genes including PIK3CA, DAPK2, TSC2, BMF, SRC, NTRK2, and NOTCH1 were identified as the core anoikis genes. Our findings provide new perspectives for exploring the role of ECM in chicken follicle development and lay the foundation for further revealing the regulatory network of follicular development.
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Affiliation(s)
- Xuelian Li
- Key Laboratory of Agricultural Animal Genetics, Breeding and Reproduction, Ministry of Education, Wuhan, Hubei, PR China; College of Animal Science and Technology and College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei, PR China
| | - Xuliang Luo
- Key Laboratory of Agricultural Animal Genetics, Breeding and Reproduction, Ministry of Education, Wuhan, Hubei, PR China; College of Animal Science and Technology and College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei, PR China
| | - Xiaxia Zhang
- Key Laboratory of Agricultural Animal Genetics, Breeding and Reproduction, Ministry of Education, Wuhan, Hubei, PR China; College of Animal Science and Technology and College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei, PR China
| | - Yan Guo
- Key Laboratory of Agricultural Animal Genetics, Breeding and Reproduction, Ministry of Education, Wuhan, Hubei, PR China; College of Animal Science and Technology and College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei, PR China
| | - Lu Cheng
- Key Laboratory of Agricultural Animal Genetics, Breeding and Reproduction, Ministry of Education, Wuhan, Hubei, PR China; College of Animal Science and Technology and College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei, PR China
| | - Manman Cheng
- Key Laboratory of Agricultural Animal Genetics, Breeding and Reproduction, Ministry of Education, Wuhan, Hubei, PR China; College of Animal Science and Technology and College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei, PR China
| | - Shuixin Tang
- Key Laboratory of Agricultural Animal Genetics, Breeding and Reproduction, Ministry of Education, Wuhan, Hubei, PR China; College of Animal Science and Technology and College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei, PR China
| | - Yanzhang Gong
- Key Laboratory of Agricultural Animal Genetics, Breeding and Reproduction, Ministry of Education, Wuhan, Hubei, PR China; College of Animal Science and Technology and College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei, PR China.
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Atia GA, Abdal Dayem A, Taher ES, Alghonemy WY, Cho SG, Aldarmahi AA, Haque MA, Alshambky A, Taymour N, Ibrahim AM, Zaghamir DE, Elmorsy EM, Hetta HF, Mohamed ME, Abass KS, Khanday S, Abdeen A. Urine-derived stem cells: a sustainable resource for advancing personalized medicine and dental regeneration. Front Bioeng Biotechnol 2025; 13:1571066. [PMID: 40357329 PMCID: PMC12066649 DOI: 10.3389/fbioe.2025.1571066] [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: 02/05/2025] [Accepted: 04/07/2025] [Indexed: 05/15/2025] Open
Abstract
Urine-based therapy, an ancient practice, has been utilized across numerous civilizations to address a wide range of ailments. Urine was considered a priceless resource in numerous traditional therapeutic applications due to its reported medicinal capabilities. While the utilization of urine treatment is contentious and lacks significant support from modern healthcare, the discovery of urine-derived stem cells (UDSCs) has introduced a promising avenue for cell-based therapy. UDSCs offer a noninvasive and easily repeatable collection method, making them a practical and viable option for therapeutic applications. Research has shown that UDSCs contribute to organ preservation by promoting revascularization and decreasing inflammatory reactions in many diseases and conditions. This review will outline the contemporary status of UDSCs research and explore their potential applications in both fundamental science and medical practice.
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Affiliation(s)
- Gamal A. Atia
- Department of Oral Medicine, Periodontology, and Diagnosis, Faculty of Dentistry, Suez Canal University, Ismailia, Egypt
| | - Ahmed Abdal Dayem
- Department of Stem Cell and Regenerative Biotechnology, School of Advanced Biotechnology, Molecular & Cellular Reprogramming Center, Institute of Advanced Regenerative Science, and Institute of Health, Aging & Society, Konkuk University, Seoul, Republic of Korea
| | - Ehab S. Taher
- Department of Basic and Clinical Medical Sciences, Faculty of Dentistry, Zarqa University, Zarqa, Jordan
| | - Wafaa Y. Alghonemy
- Department of Basic and Clinical Medical Sciences, Faculty of Dentistry, Zarqa University, Zarqa, Jordan
| | - Ssang-Goo Cho
- Department of Stem Cell and Regenerative Biotechnology, School of Advanced Biotechnology, Molecular & Cellular Reprogramming Center, Institute of Advanced Regenerative Science, and Institute of Health, Aging & Society, Konkuk University, Seoul, Republic of Korea
- R&D Team, StemExOne Co., Ltd., Seoul, Republic of Korea
| | - Ahmed A. Aldarmahi
- Department of Basic Science, College of Science and Health Professions, King Saud bin Abdulaziz University for Health Sciences, Jeddah, Saudi Arabia
- National Guard- Health Affairs, King Abdullah International Medical Research Centre, Jeddah, Saudi Arabia
| | - Md Azizul Haque
- Department of Biotechnology, Yeungnam University, Gyeongsan, Republic of Korea
| | - Abeer Alshambky
- Molecular Therapeutics Program, Fox Chase Cancer Center, Temple University, Philadelphia, PA, United States
- Department of Biochemistry, Animal Health Research Institute, Cairo, Egypt
| | - Noha Taymour
- Department of Substitutive Dental Sciences, College of Dentistry, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia
| | - Ateya M. Ibrahim
- College of Nursing, Prince Sattam bin Abdulaziz University, Al-Kharj, Saudi Arabia
| | - Donia E. Zaghamir
- College of Nursing, Prince Sattam bin Abdulaziz University, Al-Kharj, Saudi Arabia
| | - Ekramy M. Elmorsy
- Center for Health Research, Northern Border University, Arar, Saudi Arabia
| | - Helal F. Hetta
- Department of Natural Products and Alternative Medicine, Faculty of Pharmacy, University of Tabuk, Tabuk, Saudi Arabia
| | - Mohamed E. Mohamed
- Department of Basic Medical Sciences, College of Medicine, AlMaarefa University, Riyadh, Saudi Arabia
| | - Kasim S. Abass
- Department of Physiology, Biochemistry, and Pharmacology, College of Veterinary Medicine, University of Kirkuk, Kirkuk, Iraq
| | - Shifan Khanday
- Department of Biomedical Sciences, Dubai Medical College for Girls, Dubai Medical University, Dubai, United Arab Emirates
| | - Ahmed Abdeen
- Department of Forensic Medicine and Toxicology, Faculty of Veterinary Medicine, Benha University, Toukh, Egypt
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Yang HS, Zheng YX, Bai X, He XY, Wang TH. Application prospects of urine-derived stem cells in neurological and musculoskeletal diseases. World J Orthop 2024; 15:918-931. [PMID: 39473520 DOI: 10.5312/wjo.v15.i10.918] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/24/2024] [Revised: 08/25/2024] [Accepted: 09/09/2024] [Indexed: 10/11/2024] Open
Abstract
Urine-derived stem cells (USCs) are derived from urine and harbor the potential of proliferation and multidirectional differentiation. Moreover, USCs could be reprogrammed into pluripotent stem cells [namely urine-derived induced pluripotent stem cells (UiPSCs)] through transcription factors, such as octamer binding transcription factor 4, sex determining region Y-box 2, kruppel-like factor 4, myelocytomatosis oncogene, and Nanog homeobox and protein lin-28, in which the first four are known as Yamanaka factors. Mounting evidence supports that USCs and UiPSCs possess high potential of neurogenic, myogenic, and osteogenic differentiation, indicating that they may play a crucial role in the treatment of neurological and musculoskeletal diseases. Therefore, we summarized the origin and physiological characteristics of USCs and UiPSCs and their therapeutic application in neurological and musculoskeletal disorders in this review, which not only contributes to deepen our understanding of hallmarks of USCs and UiPSCs but also provides the theoretical basis for the treatment of neurological and musculoskeletal disorders with USCs and UiPSCs.
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Affiliation(s)
- Hui-Si Yang
- Department of Neurology and National Traditional Chinese Medicine Clinical Research Base, The Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, Luzhou 646000, Sichuan Province, China
| | - Yue-Xiang Zheng
- Department of Neurology and National Traditional Chinese Medicine Clinical Research Base, The Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, Luzhou 646000, Sichuan Province, China
| | - Xue Bai
- Department of Neurology and National Traditional Chinese Medicine Clinical Research Base, The Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, Luzhou 646000, Sichuan Province, China
| | - Xiu-Ying He
- Department of Anesthesiology, Institute of Neurological Disease, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
| | - Ting-Hua Wang
- Department of Neurology and National Traditional Chinese Medicine Clinical Research Base, The Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, Luzhou 646000, Sichuan Province, China
- Department of Anesthesiology, Institute of Neurological Disease, Translational Neuroscience Center, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
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Strecanska M, Sekelova T, Csobonyeiova M, Danisovic L, Cehakova M. Therapeutic applications of mesenchymal/medicinal stem/signaling cells preconditioned with external factors: Are there more efficient approaches to utilize their regenerative potential? Life Sci 2024; 346:122647. [PMID: 38614298 DOI: 10.1016/j.lfs.2024.122647] [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: 02/21/2024] [Revised: 03/25/2024] [Accepted: 04/10/2024] [Indexed: 04/15/2024]
Abstract
Mesenchymal/medicinal stem/signaling cells (MSCs) have emerged as a promising treatment option for various disorders. However, the donor's age, advanced stage of disease, and prolonged in vitro expansion often diminish the innate regenerative potential of MSCs. Besides that, the absence of MSCs' comprehensive "pre-admission testing" can result in the injection of cells with reduced viability and function, which may negatively affect the overall outcome of MSC-based therapies. It is, therefore, essential to develop effective strategies to improve the impaired biological performance of MSCs. This review focuses on the comprehensive characterization of various methods of external MSCs stimulation (hypoxia, heat shock, caloric restriction, acidosis, 3D culture, and application of extracellular matrix) that augment their medicinal potential. To emphasize the significance of MSCs priming, we summarize the effects of individual and combined preconditioning approaches, highlighting their impact on MSCs' response to either physiological or pathological conditions. We further investigate the synergic action of exogenous factors to maximize MSCs' therapeutic potential. Not to omit the field of tissue engineering, the application of pretreated MSCs seeded on scaffolds is discussed as well.
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Affiliation(s)
- Magdalena Strecanska
- National Institute of Rheumatic Diseases, Nabrezie I. Krasku 4, 921 12 Piestany, Slovakia; Institute of Medical Biology, Genetics and Clinical Genetics, Faculty of Medicine, Comenius University Bratislava, Sasinkova 4, 811 08 Bratislava, Slovakia.
| | - Tatiana Sekelova
- National Institute of Rheumatic Diseases, Nabrezie I. Krasku 4, 921 12 Piestany, Slovakia; Institute of Medical Biology, Genetics and Clinical Genetics, Faculty of Medicine, Comenius University Bratislava, Sasinkova 4, 811 08 Bratislava, Slovakia.
| | - Maria Csobonyeiova
- Institute of Histology and Embryology, Faculty of Medicine, Comenius University Bratislava, Sasinkova 4, 811 08 Bratislava, Slovakia.
| | - Lubos Danisovic
- National Institute of Rheumatic Diseases, Nabrezie I. Krasku 4, 921 12 Piestany, Slovakia; Institute of Medical Biology, Genetics and Clinical Genetics, Faculty of Medicine, Comenius University Bratislava, Sasinkova 4, 811 08 Bratislava, Slovakia.
| | - Michaela Cehakova
- Institute of Medical Biology, Genetics and Clinical Genetics, Faculty of Medicine, Comenius University Bratislava, Sasinkova 4, 811 08 Bratislava, Slovakia.
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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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Kim SH, Lee SH, Jin JA, So HJ, Lee JU, Ji MJ, Kwon EJ, Han PS, Lee HK, Kang TW. In vivo safety and biodistribution profile of Klotho-enhanced human urine-derived stem cells for clinical application. Stem Cell Res Ther 2023; 14:355. [PMID: 38072946 PMCID: PMC10712141 DOI: 10.1186/s13287-023-03595-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/20/2023] [Accepted: 11/30/2023] [Indexed: 12/18/2023] Open
Abstract
BACKGROUND Urine-derived stem cells (UDSCs) can be easily isolated from urine and possess excellent stem cell characteristics, making them a promising source for cell therapeutics. Due to their kidney origin specificity, UDSCs are considered a superior therapeutic alternative for kidney diseases compared to other stem cells. To enhance the therapeutic potential of UDSCs, we developed a culture method that effectively boosts the expression of Klotho, a kidney-protective therapeutic factor. We also optimized the Good Manufacturing Practice (GMP) system to ensure stable and large-scale production of clinical-grade UDSCs from patient urine. In this study, we evaluated the in vivo safety and distribution of Klotho-enhanced UDSCs after intravenous administration in accordance with Good Laboratory Practice (GLP) regulations. METHODS Mortality and general symptoms were continuously monitored throughout the entire examination period. We evaluated the potential toxicity of UDSCs according to the administration dosage and frequency using clinical pathological and histopathological analyses. We quantitatively assessed the in vivo distribution and retention period of UDSCs in major organs after single and repeated administration using human Alu-based qPCR analysis. We also conducted long-term monitoring for 26 weeks to assess the potential tumorigenicity. RESULTS Klotho-enhanced UDSCs exhibited excellent homing potential, and recovered Klotho expression in injured renal tissue. Toxicologically harmful effects were not observed in all mice after a single administration of UDSCs. It was also verified that repeated administration of UDSCs did not induce significant toxicological or immunological adverse effects in all mice. Single and repeated administrated UDSCs persisted in the blood and major organs for approximately 3 days and cleared in most organs, except the lungs, within 2 weeks. UDSCs that remained in the lungs were cleared out in approximately 4-5 weeks. There were no significant differences according to the variation of sex and administration frequency. The tumors were found in the intravenous administration group but they were confirmed to be non-human origin. Based on these results, it was clarified that UDSCs have no tumorigenic potential. CONCLUSIONS Our results demonstrate that Klotho-enhanced UDSCs can be manufactured as cell therapeutics through an optimized GMP procedure, and they can be safely administered without causing toxicity and tumorigenicity.
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Affiliation(s)
- Sang-Heon Kim
- Institute of Cell Biology and Regenerative Medicine, EHLBio Co., Ltd., Uiwang-si, 16006, Republic of Korea
| | - Sung-Hoon Lee
- Institute of Cell Biology and Regenerative Medicine, EHLBio Co., Ltd., Uiwang-si, 16006, Republic of Korea
| | - Jeong-Ah Jin
- Institute of Cell Biology and Regenerative Medicine, EHLBio Co., Ltd., Uiwang-si, 16006, Republic of Korea
| | - Hyung-Joon So
- Institute of Cell Biology and Regenerative Medicine, EHLBio Co., Ltd., Uiwang-si, 16006, Republic of Korea
| | - Jae-Ung Lee
- Institute of Cell Biology and Regenerative Medicine, EHLBio Co., Ltd., Uiwang-si, 16006, Republic of Korea
| | - Min-Jae Ji
- Institute of Cell Biology and Regenerative Medicine, EHLBio Co., Ltd., Uiwang-si, 16006, Republic of Korea
| | | | | | - Hong-Ki Lee
- Institute of Cell Biology and Regenerative Medicine, EHLBio Co., Ltd., Uiwang-si, 16006, Republic of Korea.
- EHLCell Clinic, Seoul, 06029, Republic of Korea.
| | - Tae-Wook Kang
- Institute of Cell Biology and Regenerative Medicine, EHLBio Co., Ltd., Uiwang-si, 16006, Republic of Korea.
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Strecanska M, Danisovic L, Ziaran S, Cehakova M. The Role of Extracellular Matrix and Hydrogels in Mesenchymal Stem Cell Chondrogenesis and Cartilage Regeneration. LIFE (BASEL, SWITZERLAND) 2022; 12:life12122066. [PMID: 36556431 PMCID: PMC9784885 DOI: 10.3390/life12122066] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 11/18/2022] [Revised: 12/02/2022] [Accepted: 12/06/2022] [Indexed: 12/13/2022]
Abstract
Diseases associated with articular cartilage disintegration or loss are still therapeutically challenging. The traditional treatment approaches only alleviate the symptoms while potentially causing serious side effects. The limited self-renewal potential of articular cartilage provides opportunities for advanced therapies involving mesenchymal stem cells (MSCs) that are characterized by a remarkable regenerative capacity. The chondrogenic potential of MSCs is known to be regulated by the local environment, including soluble factors and the less discussed extracellular matrix (ECM) components. This review summarizes the process of chondrogenesis, and also the biological properties of the ECM mediated by mechanotransduction as well as canonical and non-canonical signaling. Our focus is also on the influence of the ECM's physical parameters, molecular composition, and chondrogenic factor affinity on the adhesion, survival, and chondrogenic differentiation of MSCs. These basic biological insights are crucial for a more precise fabrication of ECM-mimicking hydrogels to improve cartilage tissue reconstruction. Lastly, we provide an overview of hydrogel classification and characterization. We also include the results from preclinical models combining MSCs with hydrogels for the treatment of cartilage defects, to support clinical application of this construct. Overall, it is believed that the proper combination of MSCs, hydrogels, and chondrogenic factors can lead to complex cartilage regeneration.
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Affiliation(s)
- Magdalena Strecanska
- National Institute of Rheumatic Diseases, Nabrezie I. Krasku 4, 921 12 Piestany, Slovakia
- Institute of Medical Biology, Genetics, and Clinical Genetics, Faculty of Medicine, Comenius University, Sasinkova 4, 811 08 Bratislava, Slovakia
| | - Lubos Danisovic
- National Institute of Rheumatic Diseases, Nabrezie I. Krasku 4, 921 12 Piestany, Slovakia
- Institute of Medical Biology, Genetics, and Clinical Genetics, Faculty of Medicine, Comenius University, Sasinkova 4, 811 08 Bratislava, Slovakia
| | - Stanislav Ziaran
- National Institute of Rheumatic Diseases, Nabrezie I. Krasku 4, 921 12 Piestany, Slovakia
- Department of Urology, Faculty of Medicine, Comenius University, Limbova 5, 833 05 Bratislava, Slovakia
| | - Michaela Cehakova
- National Institute of Rheumatic Diseases, Nabrezie I. Krasku 4, 921 12 Piestany, Slovakia
- Institute of Medical Biology, Genetics, and Clinical Genetics, Faculty of Medicine, Comenius University, Sasinkova 4, 811 08 Bratislava, Slovakia
- Correspondence: ; Tel.: +421-2-5935-7215
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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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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: 15] [Impact Index Per Article: 5.0] [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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10
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Zhang W, Hu J, Huang Y, Wu C, Xie H. Urine-derived stem cells: applications in skin, bone and articular cartilage repair. BURNS & TRAUMA 2021; 9:tkab039. [PMID: 34859109 PMCID: PMC8633594 DOI: 10.1093/burnst/tkab039] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/16/2021] [Revised: 09/18/2021] [Indexed: 02/05/2023]
Abstract
As an emerging type of adult stem cell featuring non-invasive acquisition, urine-derived stem cells (USCs) have shown great potential for applications in tissue engineering and regenerative medicine. With a growing amount of research on the topic, the effectiveness of USCs in various disease models has been shown and the underlying mechanisms have also been explored, though many aspects still remain unclear. In this review, we aim to provide an up-to-date overview of the biological characteristics of USCs and their applications in skin, bone and articular cartilage repair. In addition to the identification procedure of USCs, we also summarize current knowledge of the underlying repair mechanisms and application modes of USCs. Potential concerns and perspectives have also been summarized.
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Affiliation(s)
- Wenqian Zhang
- Laboratory of Stem Cell and Tissue Engineering, Orthopedic Research Institute, Med-X Center for Materials, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China
| | - Jungen Hu
- Laboratory of Stem Cell and Tissue Engineering, Orthopedic Research Institute, Med-X Center for Materials, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China
| | - Yizhou Huang
- Laboratory of Stem Cell and Tissue Engineering, Orthopedic Research Institute, Med-X Center for Materials, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China
| | - Chenyu Wu
- Laboratory of Stem Cell and Tissue Engineering, Orthopedic Research Institute, Med-X Center for Materials, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China
| | - Huiqi Xie
- Laboratory of Stem Cell and Tissue Engineering, Orthopedic Research Institute, Med-X Center for Materials, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China
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11
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Burdeyron P, Giraud S, Hauet T, Steichen C. Urine-derived stem/progenitor cells: A focus on their characterization and potential. World J Stem Cells 2020; 12:1080-1096. [PMID: 33178393 PMCID: PMC7596444 DOI: 10.4252/wjsc.v12.i10.1080] [Citation(s) in RCA: 26] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/29/2020] [Revised: 06/26/2020] [Accepted: 08/24/2020] [Indexed: 02/06/2023] Open
Abstract
Cell therapy, i.e., the use of cells to repair an affected tissue or organ, is at the forefront of regenerative and personalized medicine. Among the multiple cell types that have been used for this purpose [including adult stem cells such as mesenchymal stem cells or pluripotent stem cells], urine-derived stem cells (USCs) have aroused interest in the past years. USCs display classical features of mesenchymal stem cells such as differentiation capacity and immunomodulation. Importantly, they have the main advantage of being isolable from one sample of voided urine with a cheap and unpainful procedure, which is broadly applicable, whereas most adult stem cell types require invasive procedure. Moreover, USCs can be differentiated into renal cell types. This is of high interest for renal cell therapy-based regenerative approaches. This review will firstly describe the isolation and characterization of USCs. We will specifically present USC phenotype, which is not an object of consensus in the literature, as well as detail their differentiation capacity. In the second part of this review, we will present and discuss the main applications of USCs. These include use as a substrate to generate human induced pluripotent stem cells, but we will deeply focus on the use of USCs for cell therapy approaches with a detailed analysis depending on the targeted organ or system. Importantly, we will also focus on the applications that rely on the use of USC-derived products such as microvesicles including exosomes, which is a strategy being increasingly employed. In the last section, we will discuss the remaining barriers and challenges in the field of USC-based regenerative medicine.
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Affiliation(s)
- Perrine Burdeyron
- INSERM U1082 IRTOMIT, CHU de Poitiers, Poitiers 86021, France
- Faculté de Médecine et Pharmacie, Université de Poitiers, Poitiers 86021, France
| | - Sébastien Giraud
- INSERM U1082 IRTOMIT, CHU de Poitiers, Poitiers 86021, France
- Service de Biochimie, CHU de Poitiers, Poitiers 86021, France
| | - Thierry Hauet
- INSERM U1082 IRTOMIT, CHU de Poitiers, Poitiers 86021, France
- Faculté de Médecine et Pharmacie, Université de Poitiers, Poitiers 86021, France
- Service de Biochimie, CHU de Poitiers, Poitiers 86021, France
| | - Clara Steichen
- INSERM U1082 IRTOMIT, CHU de Poitiers, Poitiers 86021, France
- Faculté de Médecine et Pharmacie, Université de Poitiers, Poitiers 86021, France.
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12
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Choi JY, Chun SY, Ha YS, Kim DH, Kim J, Song PH, Kim HT, Yoo ES, Kim BS, Kwon TG. Potency of Human Urine-Derived Stem Cells for Renal Lineage Differentiation. Tissue Eng Regen Med 2017; 14:775-785. [PMID: 30603527 PMCID: PMC6171660 DOI: 10.1007/s13770-017-0081-y] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/07/2017] [Revised: 09/01/2017] [Accepted: 09/03/2017] [Indexed: 01/09/2023] Open
Abstract
Kidney is one of the most difficult organs for regeneration. Several attempts have been performed to regenerate renal tissue using stem cells, the results were not satisfactory. Urine is major product of kidney and contains cells from renal components. Moreover, urine-derived stem cells (USCs) can be easily obtained without any health risks throughout a patient's entire life. Here, we evaluated the utility of USCs for renal tissue regeneration. In this study, the ability of USCs to differentiate into renal lineage cells was compared with that of adipose tissue-derived stem cells (ADSCs) and amniotic fluid-derived stem cells (AFSCs), with respect to surface antigen expression, morphology, immunocytochemistry, renal lineage gene expression, secreted factors, immunomodulatory marker expression, in vivo safety, and renal differentiation potency. Undifferentiated USCs were positive for CD44 and CD73, negative for CD34 and CD45, and formed aggregates after 3 weeks of renal differentiation. Undifferentiated USCs showed high SSEA4 expression, while renal-differentiated cells expressed PAX2, WT1, and CADHERIN 6. In the stem/renal lineage-associated gene analysis, OCT4, SSEA4, and CD117 were significantly downregulated over time, while PAX2, LIM1, PDGFRA, E-CADHERIN, CD24, ACTB, AQP1, OCLN, and NPHS1 were gradually upregulated. In the in vivo safety evaluation, renal-differentiated USCs did not show abnormal histology. These findings demonstrated that USCs have a similar MSC potency, renal lineage-differentiation ability, immunomodulatory effects, and in vivo safety as ADSCs and AFSCs, and showed higher levels of growth factor secretion for paracrine effects. Therefore, urine and USCs can be one of good cell sources for kidney regeneration.
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Affiliation(s)
- Jae Young Choi
- Department of Urology, College of Medicine, Yeungnam University, 170 Hyunchung-ro, Nam-gu, Daegu, 42415 Korea
| | - So Young Chun
- Biomedical Research Institute, Kyungpook National University Hospital, 130 Dongdeok-ro, Jung-gu, Daegu, 41944 Korea
| | - Yun-Sok Ha
- Department of Urology, School of Medicine, Kyungpook National University, 130 Dongdeok-ro, Jung-gu, Daegu, 41944 Korea
| | - Dae Hwan Kim
- Department of Laboratory Animal Research Support Team, Yeungnam University Medical Center, 170 Hyunchung-ro, Nam-gu, Daegu, 42415 Korea
| | - Jeongshik Kim
- Department of Pathology, Central Hospital, 480 Munsu-ro, Nam-gu, Ulsan, 44667 Korea
| | - Phil Hyun Song
- Department of Urology, College of Medicine, Yeungnam University, 170 Hyunchung-ro, Nam-gu, Daegu, 42415 Korea
| | - Hyun Tae Kim
- Department of Urology, School of Medicine, Kyungpook National University, 130 Dongdeok-ro, Jung-gu, Daegu, 41944 Korea
| | - Eun Sang Yoo
- Department of Urology, School of Medicine, Kyungpook National University, 130 Dongdeok-ro, Jung-gu, Daegu, 41944 Korea
| | - Bum Soo Kim
- Department of Urology, School of Medicine, Kyungpook National University, 130 Dongdeok-ro, Jung-gu, Daegu, 41944 Korea
| | - Tae Gyun Kwon
- Department of Urology, School of Medicine, Kyungpook National University, 130 Dongdeok-ro, Jung-gu, Daegu, 41944 Korea
- Department of Urology, Kyungpook National University Chilgok Hospital, 807 Hogukro, Buk-gu, Daegu, 41404 Korea
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