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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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Bejoy J, Welch RC, Qian ES, Williams FM, Gibson-Corley KN, Wilson MH, Paragas N, Woodard LE. Urine-derived stem cells display homing, incorporation, and regeneration in human organoid and mouse models of acute kidney injury. Mol Ther 2025:S1525-0016(25)00219-9. [PMID: 40158205 DOI: 10.1016/j.ymthe.2025.03.044] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/27/2024] [Revised: 11/03/2024] [Accepted: 03/25/2025] [Indexed: 04/02/2025] Open
Abstract
Urine-derived stem cells (USCs) are adult human stem cells that can be collected noninvasively from urine and cultured in vitro. Because of their renal origin and reported therapeutic effects, we hypothesized that USCs would home to the injured kidney in acute kidney injury (AKI) models. We used mouse models of glycerol-induced rhabdomyolysis or unilateral nephrectomy with clamping ischemia reperfusion injury to model AKI. To track USC homing by live animal imaging, we administered luciferase-expressing (Luc) USCs to mice by intraperitoneal injection. We observed USC localization to both the tubules and glomeruli of injured mice within 3 h by histology. We confirmed the presence of Luc-USCs in the kidney at 3 h, 24 h, and 48 h after the injection using biodistribution analysis of quantitative bioluminescence tomography imaging. We performed immunostaining for kidney injury molecule-1 (KIM-1/HAVCR1/TIM-1) for kidney injury and found reduced expression in USC-treated group at 24 h after injection. To evaluate the effects of the human USCs on injured human nephrons, we injured human kidney organoids with the nephrotoxin cisplatin (5 μM) followed by 5 × 104 USC treatment. USCs were incorporated and lowered expression of KIM-1 in the organoids. USCs home to injured nephrons and reduce measures of kidney injury.
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Affiliation(s)
- Julie Bejoy
- Department of Medicine, Division of Nephrology and Hypertension, Vanderbilt University Medical Center, Nashville, TN 37232, USA
| | - Richard C Welch
- Department of Medicine, Division of Nephrology and Hypertension, Vanderbilt University Medical Center, Nashville, TN 37232, USA
| | - Eddie S Qian
- Department of Medicine, Division of Nephrology and Hypertension, Vanderbilt University Medical Center, Nashville, TN 37232, USA
| | - Felisha M Williams
- Department of Medicine, Division of Nephrology and Hypertension, Vanderbilt University Medical Center, Nashville, TN 37232, USA
| | - Katherine N Gibson-Corley
- Department of Medicine, Division of Pathology, Microbiology & Immunology, Vanderbilt University Medical Center, Nashville, TN 37232, USA; Department of Medicine, Comparative Pathology and Research Histology, Vanderbilt University Medical Center, Nashville, TN 37232, USA
| | - Matthew H Wilson
- Department of Medicine, Division of Nephrology and Hypertension, Vanderbilt University Medical Center, Nashville, TN 37232, USA; Department of Veterans Affairs, Nashville, TN 37212, USA; Departments of Pharmacology and Cell and Developmental Biology, Vanderbilt University, Nashville, TN 37232, USA
| | - Neal Paragas
- Department of Radiology, University of Washington, Seattle, WA 98109, USA
| | - Lauren E Woodard
- Department of Medicine, Division of Nephrology and Hypertension, Vanderbilt University Medical Center, Nashville, TN 37232, USA; Department of Veterans Affairs, Nashville, TN 37212, USA; Department of Biomedical Engineering, Vanderbilt University, Nashville, TN 37232, USA.
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Heyman E, Olenic M, De Vlieghere E, De Smet S, Devriendt B, Thorrez L, De Schauwer C. Donor age and breed determine mesenchymal stromal cell characteristics. Stem Cell Res Ther 2025; 16:99. [PMID: 40022193 PMCID: PMC11871689 DOI: 10.1186/s13287-025-04236-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/04/2024] [Accepted: 02/17/2025] [Indexed: 03/03/2025] Open
Abstract
BACKGROUND Mesenchymal stromal cells (MSCs) hold significant potential for various applications in regenerative medicine and tissue engineering. Initially considered as a single cell type with defined characteristics, MSCs are now known as a heterogeneous cell population with remarkable differences in their properties. No consensus exists on how donor age affects MSC characteristics, like proliferation. Additionally, differences in differentiation capacities and immunophenotype could arise when MSCs are isolated from different animals breeds, which is relevant for experimental and preclinical studies of MSC-based treatments. METHODS In this study, we isolated bovine adipose tissue-derived MSCs from three age categories, i.e. fetal, calf, and adult, and of two different breeds, i.e. Holstein Friesian (HF) and Belgian Blue (BB). MSC characterization included tri-lineage differentiation, proliferation and senescence assays, and immunophenotyping using multi-color flow cytometry. RESULTS Especially fetal and calf HF-MSCs showed a high proliferation capacity, where 4 and 6 out of 7 donors, respectively, could surpass 30 population doublings. Adipogenic differentiation potential was higher for fetal and adult HF-MSCs. Furthermore, breed, but not age, affected their osteogenic differentiation potential, with BB-MSCs performing better. Evaluation of cell surface marker expression revealed a breed effect, as calf HF-MSCs showed a higher percentage of Cluster of Differentiation (CD)34+ cells compared to calf BB-MSCs, which was correlated with both osteogenic differentiation and proliferation potential. CONCLUSIONS Our findings clearly show the impact of donor characteristics such as age and breed on MSC proliferation, immunophenotype, and differentiation potential, illustrating the importance of selecting the appropriate MSC donor for MSC-based treatments when allogeneic MSCs are considered.
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Affiliation(s)
- Emma Heyman
- Veterinary Stem Cell Research Unit, Ghent University, Merelbeke, Belgium
| | - Maria Olenic
- Veterinary Stem Cell Research Unit, Ghent University, Merelbeke, Belgium
- Tissue Engineering Lab, Department of Development and Regeneration, KU Leuven Campus Kulak, Kortrijk, Belgium
| | - Elly De Vlieghere
- Tissue Engineering Lab, Department of Development and Regeneration, KU Leuven Campus Kulak, Kortrijk, Belgium
- Polymer Chemistry and Biomaterials Group, Centre of Macromolecular Chemistry, Ghent University, Ghent, Belgium
| | - Stefaan De Smet
- Laboratory for Animal Nutrition and Animal Product Quality, Department of Animal Sciences and Aquatic Ecology, Ghent University, Ghent, Belgium
| | - Bert Devriendt
- Laboratory of Immunology, Department of Translational Physiology, Infectiology and Public Health, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium
| | - Lieven Thorrez
- Tissue Engineering Lab, Department of Development and Regeneration, KU Leuven Campus Kulak, Kortrijk, Belgium
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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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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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Zhou JP, Peng SS, Xu J, Cheng XW, Wang XH, Tao JL, Dai HW, Cao X. Exploring the therapeutic potential of urine-derived stem cell exosomes in temporomandibular joint osteoarthritis. FASEB J 2024; 38:e23852. [PMID: 39101942 DOI: 10.1096/fj.202400448rr] [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: 02/28/2024] [Revised: 07/15/2024] [Accepted: 07/21/2024] [Indexed: 08/06/2024]
Abstract
Temporomandibular joint osteoarthritis (TMJOA) is a degenerative ailment that causes slow cartilage degeneration, aberrant bone remodeling, and persistent discomfort, leading to a considerable reduction in the patient's life quality. Current treatment options for TMJOA have limited efficacy. This investigation aimed to explore a potential strategy for halting or reversing the progression of TMJOA through the utilization of exosomes (EXOs) derived from urine-derived stem cells (USCs). The USC-EXOs were obtained through microfiltration and ultrafiltration techniques, followed by their characterization using particle size analysis, electron microscopy, and immunoblotting. Subsequently, an in vivo model of TMJOA induced by mechanical force was established. To assess the changes in the cartilage of TMJOA treated with USC-EXOs, we performed histology analysis using hematoxylin-eosin staining, immunohistochemistry, and histological scoring. Our findings indicate that the utilization of USC-EXOs yields substantial reductions in TMJOA, while concurrently enhancing the structural integrity and smoothness of the compromised condylar cartilage surface. Additionally, USC-EXOs exhibit inhibitory effects on osteoclastogenic activity within the subchondral bone layer of the condylar cartilage, as well as attenuated apoptosis in the rat TMJ in response to mechanical injury. In conclusion, USC-EXOs hold considerable promise as a potential therapeutic intervention for TMJOA.
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Affiliation(s)
- Jian-Ping Zhou
- College of Stomatology, Chongqing Medical University, Chongqing, China
- Chongqing Key Laboratory of Oral Diseases and Biomedical Sciences, Chongqing, China
- Chongqing Municipal Key Laboratory of Oral Biomedical Engineering of Higher Education, Chongqing, China
| | - Si-Si Peng
- College of Stomatology, Chongqing Medical University, Chongqing, China
- Chongqing Key Laboratory of Oral Diseases and Biomedical Sciences, Chongqing, China
- Chongqing Municipal Key Laboratory of Oral Biomedical Engineering of Higher Education, Chongqing, China
| | - Jie Xu
- College of Stomatology, Chongqing Medical University, Chongqing, China
- Chongqing Key Laboratory of Oral Diseases and Biomedical Sciences, Chongqing, China
- Chongqing Municipal Key Laboratory of Oral Biomedical Engineering of Higher Education, Chongqing, China
| | - Xing-Wang Cheng
- Department of Orthopedic Surgery, Center for Joint Surgery, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Xiao-Hui Wang
- College of Stomatology, Chongqing Medical University, Chongqing, China
- Chongqing Key Laboratory of Oral Diseases and Biomedical Sciences, Chongqing, China
- Chongqing Municipal Key Laboratory of Oral Biomedical Engineering of Higher Education, Chongqing, China
| | - Jun-Li Tao
- College of Stomatology, Chongqing Medical University, Chongqing, China
- Chongqing Key Laboratory of Oral Diseases and Biomedical Sciences, Chongqing, China
- Chongqing Municipal Key Laboratory of Oral Biomedical Engineering of Higher Education, Chongqing, China
| | - Hong-Wei Dai
- College of Stomatology, Chongqing Medical University, Chongqing, China
- Chongqing Key Laboratory of Oral Diseases and Biomedical Sciences, Chongqing, China
- Chongqing Municipal Key Laboratory of Oral Biomedical Engineering of Higher Education, Chongqing, China
| | - Xin Cao
- College of Stomatology, Chongqing Medical University, Chongqing, China
- Chongqing Key Laboratory of Oral Diseases and Biomedical Sciences, Chongqing, China
- Chongqing Municipal Key Laboratory of Oral Biomedical Engineering of Higher Education, Chongqing, 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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Sun Y, Zhao H, Yang S, Wang G, Zhu L, Sun C, An Y. Urine-derived stem cells: Promising advancements and applications in regenerative medicine and beyond. Heliyon 2024; 10:e27306. [PMID: 38509987 PMCID: PMC10951541 DOI: 10.1016/j.heliyon.2024.e27306] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/23/2023] [Revised: 02/27/2024] [Accepted: 02/27/2024] [Indexed: 03/22/2024] Open
Abstract
Currently, stem cells are a prominent focus of regenerative engineering research. However, due to the limitations of commonly used stem cell sources, their application in therapy is often restricted to the experimental stage and constrained by ethical considerations. In contrast, urine-derived stem cells (USCs) offer promising advantages for clinical trials and applications. The noninvasive nature of the collection process allows for repeated retrieval within a short period, making it a more feasible option. Moreover, studies have shown that USCs have a protective effect on organs, promoting vascular regeneration, inhibiting oxidative stress, and reducing inflammation in various acute and chronic organ dysfunctions. The application of USCs has also been enhanced by advancements in biomaterials technology, enabling better targeting and controlled release capabilities. This review aims to summarize the current state of research on USCs, providing insights for future applications in basic and clinical settings.
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Affiliation(s)
| | | | - Shuguang Yang
- Department of Critical Care Medicine, Peking University People's Hospital, PR China
| | - Guangjie Wang
- Department of Critical Care Medicine, Peking University People's Hospital, PR China
| | - Leijie Zhu
- Department of Critical Care Medicine, Peking University People's Hospital, PR China
| | - Chang Sun
- Department of Critical Care Medicine, Peking University People's Hospital, PR China
| | - Youzhong An
- Department of Critical Care Medicine, Peking University People's Hospital, PR China
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9
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Huang RL, Li Q, Ma JX, Atala A, Zhang Y. Body fluid-derived stem cells - an untapped stem cell source in genitourinary regeneration. Nat Rev Urol 2023; 20:739-761. [PMID: 37414959 PMCID: PMC11639537 DOI: 10.1038/s41585-023-00787-2] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 05/30/2023] [Indexed: 07/08/2023]
Abstract
Somatic stem cells have been obtained from solid organs and tissues, including the bone marrow, placenta, corneal stroma, periosteum, adipose tissue, dental pulp and skeletal muscle. These solid tissue-derived stem cells are often used for tissue repair, disease modelling and new drug development. In the past two decades, stem cells have also been identified in various body fluids, including urine, peripheral blood, umbilical cord blood, amniotic fluid, synovial fluid, breastmilk and menstrual blood. These body fluid-derived stem cells (BFSCs) have stemness properties comparable to those of other adult stem cells and, similarly to tissue-derived stem cells, show cell surface markers, multi-differentiation potential and immunomodulatory effects. However, BFSCs are more easily accessible through non-invasive or minimally invasive approaches than solid tissue-derived stem cells and can be isolated without enzymatic tissue digestion. Additionally, BFSCs have shown good versatility in repairing genitourinary abnormalities in preclinical models through direct differentiation or paracrine mechanisms such as pro-angiogenic, anti-apoptotic, antifibrotic, anti-oxidant and anti-inflammatory effects. However, optimization of protocols is needed to improve the efficacy and safety of BFSC therapy before therapeutic translation.
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Affiliation(s)
- Ru-Lin Huang
- Department of Plastic and Reconstructive Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Qingfeng Li
- Department of Plastic and Reconstructive Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Jian-Xing Ma
- Department of Biochemistry, Wake Forest School of Medicine, Winston-Salem, NC, USA
| | - Anthony Atala
- Institute for Regenerative Medicine, Wake Forest School of Medicine, Winston-Salem, NC, USA
| | - Yuanyuan Zhang
- Institute for Regenerative Medicine, Wake Forest School of Medicine, Winston-Salem, NC, USA.
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10
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Carvalho S, Santos JI, Moreira L, Gonçalves M, David H, Matos L, Encarnação M, Alves S, Coutinho MF. Neurological Disease Modeling Using Pluripotent and Multipotent Stem Cells: A Key Step towards Understanding and Treating Mucopolysaccharidoses. Biomedicines 2023; 11:biomedicines11041234. [PMID: 37189853 DOI: 10.3390/biomedicines11041234] [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: 03/08/2023] [Revised: 04/18/2023] [Accepted: 04/19/2023] [Indexed: 05/17/2023] Open
Abstract
Despite extensive research, the links between the accumulation of glycosaminoglycans (GAGs) and the clinical features seen in patients suffering from various forms of mucopolysaccharidoses (MPSs) have yet to be further elucidated. This is particularly true for the neuropathology of these disorders; the neurological symptoms are currently incurable, even in the cases where a disease-specific therapeutic approach does exist. One of the best ways to get insights on the molecular mechanisms driving that pathogenesis is the analysis of patient-derived cells. Yet, not every patient-derived cell recapitulates relevant disease features. For the neuronopathic forms of MPSs, for example, this is particularly evident because of the obvious inability to access live neurons. This scenario changed significantly with the advent of induced pluripotent stem cell (iPSC) technologies. From then on, a series of differentiation protocols to generate neurons from iPSC was developed and extensively used for disease modeling. Currently, human iPSC and iPSC-derived cell models have been generated for several MPSs and numerous lessons were learnt from their analysis. Here we review most of those studies, not only listing the currently available MPS iPSC lines and their derived models, but also summarizing how they were generated and the major information different groups have gathered from their analyses. Finally, and taking into account that iPSC generation is a laborious/expensive protocol that holds significant limitations, we also hypothesize on a tempting alternative to establish MPS patient-derived neuronal cells in a much more expedite way, by taking advantage of the existence of a population of multipotent stem cells in human dental pulp to establish mixed neuronal and glial cultures.
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Affiliation(s)
- Sofia Carvalho
- Research and Development Unit, Department of Human Genetics, National Institute of Health Doutor Ricardo Jorge, INSA I.P., Rua Alexandre Herculano, 321, 4000-055 Porto, Portugal
- Center for the Study of Animal Science-Instituto de Ciências, Tecnologias e Agroambiente da Universidade do Porto, CECA-ICETA, University of Porto, Praça Gomes Teixeira, Apartado 55142, 4051-401 Porto, Portugal
- Associate Laboratory for Animal and Veterinary Sciences, AL4AnimalS, Faculdade de Medicina Veterinária Avenida da Universidade Técnica, 1300-477 Lisboa, Portugal
- Faculty of Pharmacy, University of Coimbra, Polo das Ciências da Saúde, Azinhaga de SantaComba, 3000-548 Coimbra, Portugal
| | - Juliana Inês Santos
- Research and Development Unit, Department of Human Genetics, National Institute of Health Doutor Ricardo Jorge, INSA I.P., Rua Alexandre Herculano, 321, 4000-055 Porto, Portugal
- Center for the Study of Animal Science-Instituto de Ciências, Tecnologias e Agroambiente da Universidade do Porto, CECA-ICETA, University of Porto, Praça Gomes Teixeira, Apartado 55142, 4051-401 Porto, Portugal
- Associate Laboratory for Animal and Veterinary Sciences, AL4AnimalS, Faculdade de Medicina Veterinária Avenida da Universidade Técnica, 1300-477 Lisboa, Portugal
- Biology Department, Faculty of Sciences, University of Porto, Rua do Campo Alegre, 4169-007 Porto, Portugal
| | - Luciana Moreira
- Research and Development Unit, Department of Human Genetics, National Institute of Health Doutor Ricardo Jorge, INSA I.P., Rua Alexandre Herculano, 321, 4000-055 Porto, Portugal
- Center for the Study of Animal Science-Instituto de Ciências, Tecnologias e Agroambiente da Universidade do Porto, CECA-ICETA, University of Porto, Praça Gomes Teixeira, Apartado 55142, 4051-401 Porto, Portugal
- Associate Laboratory for Animal and Veterinary Sciences, AL4AnimalS, Faculdade de Medicina Veterinária Avenida da Universidade Técnica, 1300-477 Lisboa, Portugal
| | - Mariana Gonçalves
- Research and Development Unit, Department of Human Genetics, National Institute of Health Doutor Ricardo Jorge, INSA I.P., Rua Alexandre Herculano, 321, 4000-055 Porto, Portugal
- Center for the Study of Animal Science-Instituto de Ciências, Tecnologias e Agroambiente da Universidade do Porto, CECA-ICETA, University of Porto, Praça Gomes Teixeira, Apartado 55142, 4051-401 Porto, Portugal
- Associate Laboratory for Animal and Veterinary Sciences, AL4AnimalS, Faculdade de Medicina Veterinária Avenida da Universidade Técnica, 1300-477 Lisboa, Portugal
- Centre for the Research and Technology of Agro-Environmental and Biological Sciences, CITAB, Inov4Agro, University of Trás-os-Montes and Alto Douro, 5000-801 Vila Real, Portugal
| | - Hugo David
- Research and Development Unit, Department of Human Genetics, National Institute of Health Doutor Ricardo Jorge, INSA I.P., Rua Alexandre Herculano, 321, 4000-055 Porto, Portugal
- Center for the Study of Animal Science-Instituto de Ciências, Tecnologias e Agroambiente da Universidade do Porto, CECA-ICETA, University of Porto, Praça Gomes Teixeira, Apartado 55142, 4051-401 Porto, Portugal
- Associate Laboratory for Animal and Veterinary Sciences, AL4AnimalS, Faculdade de Medicina Veterinária Avenida da Universidade Técnica, 1300-477 Lisboa, Portugal
- Biology Department, Faculty of Sciences, University of Porto, Rua do Campo Alegre, 4169-007 Porto, Portugal
| | - Liliana Matos
- Research and Development Unit, Department of Human Genetics, National Institute of Health Doutor Ricardo Jorge, INSA I.P., Rua Alexandre Herculano, 321, 4000-055 Porto, Portugal
- Center for the Study of Animal Science-Instituto de Ciências, Tecnologias e Agroambiente da Universidade do Porto, CECA-ICETA, University of Porto, Praça Gomes Teixeira, Apartado 55142, 4051-401 Porto, Portugal
- Associate Laboratory for Animal and Veterinary Sciences, AL4AnimalS, Faculdade de Medicina Veterinária Avenida da Universidade Técnica, 1300-477 Lisboa, Portugal
| | - Marisa Encarnação
- Research and Development Unit, Department of Human Genetics, National Institute of Health Doutor Ricardo Jorge, INSA I.P., Rua Alexandre Herculano, 321, 4000-055 Porto, Portugal
- Center for the Study of Animal Science-Instituto de Ciências, Tecnologias e Agroambiente da Universidade do Porto, CECA-ICETA, University of Porto, Praça Gomes Teixeira, Apartado 55142, 4051-401 Porto, Portugal
- Associate Laboratory for Animal and Veterinary Sciences, AL4AnimalS, Faculdade de Medicina Veterinária Avenida da Universidade Técnica, 1300-477 Lisboa, Portugal
| | - Sandra Alves
- Research and Development Unit, Department of Human Genetics, National Institute of Health Doutor Ricardo Jorge, INSA I.P., Rua Alexandre Herculano, 321, 4000-055 Porto, Portugal
- Center for the Study of Animal Science-Instituto de Ciências, Tecnologias e Agroambiente da Universidade do Porto, CECA-ICETA, University of Porto, Praça Gomes Teixeira, Apartado 55142, 4051-401 Porto, Portugal
- Associate Laboratory for Animal and Veterinary Sciences, AL4AnimalS, Faculdade de Medicina Veterinária Avenida da Universidade Técnica, 1300-477 Lisboa, Portugal
| | - Maria Francisca Coutinho
- Research and Development Unit, Department of Human Genetics, National Institute of Health Doutor Ricardo Jorge, INSA I.P., Rua Alexandre Herculano, 321, 4000-055 Porto, Portugal
- Center for the Study of Animal Science-Instituto de Ciências, Tecnologias e Agroambiente da Universidade do Porto, CECA-ICETA, University of Porto, Praça Gomes Teixeira, Apartado 55142, 4051-401 Porto, Portugal
- Associate Laboratory for Animal and Veterinary Sciences, AL4AnimalS, Faculdade de Medicina Veterinária Avenida da Universidade Técnica, 1300-477 Lisboa, Portugal
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11
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Zhao K, Zhou T, Yang J, Li Y, Qin J, Wang S, Li D, Chen J, Zheng WV. Lutein shows a protective effect against the aging of mesenchymal stem cells by downregulating inflammation. Int Immunopharmacol 2023. [DOI: 10.1016/j.intimp.2023.109749] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/22/2023]
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12
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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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13
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Zhang X, Chen JL, Xing F, Duan X. Three-dimensional printed polylactic acid and hydroxyapatite composite scaffold with urine-derived stem cells as a treatment for bone defects. JOURNAL OF MATERIALS SCIENCE. MATERIALS IN MEDICINE 2022; 33:71. [PMID: 36190568 PMCID: PMC9529701 DOI: 10.1007/s10856-022-06686-z] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 02/27/2022] [Accepted: 08/22/2022] [Indexed: 06/16/2023]
Abstract
Bone defects still pose various challenges in osteology. As one treatment method for bone defects, tissue engineering requires biomaterials with good biocompatibility and stem cells with good differentiation. This study aimed to fabricate a 3D-printed polylactic acid and hydroxyapatite (PLA/HA) composite scaffold with urine-derived stem cells (USCs) to study its therapeutic effect in a rat model of skull defects. USCs were isolated and extracted from the urine of healthy adult males and inoculated onto PLA/HA and PLA scaffolds fabricated by 3D printing technology. A total of 36 skull defect models in eighteen Sprague-Dawley rats were randomly divided into a control group (no treatment of the defects), PLA group (treated with PLA scaffolds with USCs), and PLA/HA group (treated with PLA/HA scaffolds with USCs). The therapeutic efficacy was evaluated by real-time PCR, microcomputed tomography (micro-CT), and immunohistochemistry at 4, 8, and 12 weeks. We found that the PLA/HA scaffold loaded with USCs effectively promoted new bone regeneration in the defect area. CT images showed that in the PLA/HA group, the defect area was almost entirely covered by newly formed bone (coverage of 96.7 ± 1.6%), and the coverage was greater than that in the PLA group (coverage of 74.6 ± 1.9%) at 12 weeks. Histology and immunohistochemical staining showed the highest new bone formation on the PLA/HA scaffolds containing USCs in the defect site at 12 weeks. These findings demonstrate the broad application prospects of PLA/HA scaffolds with USCs in bone tissue engineering. Graphical abstract.
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Affiliation(s)
- Xiang Zhang
- Department of Orthopaedics, West China Hospital, Sichuan University, No. 37 Guoxue Lane, Chengdu, 610041, Sichuan, China
| | - Jia-Lei Chen
- Department of Orthopaedics, West China Hospital, Sichuan University, No. 37 Guoxue Lane, Chengdu, 610041, Sichuan, China
| | - Fei Xing
- Department of Orthopaedics, West China Hospital, Sichuan University, No. 37 Guoxue Lane, Chengdu, 610041, Sichuan, China
| | - Xin Duan
- Department of Orthopaedics, West China Hospital, Sichuan University, No. 37 Guoxue Lane, Chengdu, 610041, Sichuan, China.
- Department of Orthopedics, Ganzi Tibetan Autonomous Prefecture People's Hospital, Ganzi Prefecture, 626700, Sichuan, 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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15
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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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16
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Li H, Fan XL, Wang YN, Lu W, Wang H, Liao R, Zeng M, Yang JX, Hu Y, Xie J. Extracellular Vesicles from Human Urine-Derived Stem Cells Ameliorate Particulate Polyethylene-Induced Osteolysis. Int J Nanomedicine 2021; 16:7479-7494. [PMID: 34785895 PMCID: PMC8579861 DOI: 10.2147/ijn.s325646] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2021] [Accepted: 10/04/2021] [Indexed: 01/27/2023] Open
Abstract
Purpose Wear debris particle-induced periprosthetic osteolysis is a severe complication of total joint replacement that results in aseptic loosening and subsequent arthroplasty failure. No effective therapeutic agents or drugs have been approved to prevent or treat osteolysis; thus, revision surgery is often needed. Extracellular vesicles (EVs) are vital nanosized regulators of intercellular communication that can be directly applied to promote tissue repair and regeneration. In this study, we assessed the therapeutic potential of EVs from human urine-derived stem cells (USCs) (USC-EVs) in preventing ultrahigh-molecular-weight polyethylene (UHMWPE) particle-induced osteolysis. Methods USCs were characterized by measuring induced multipotent differentiation and flow cytometry. USC-EVs were isolated and characterized using transmission electron microscopy (TEM), dynamic light scattering (DLS) and Western blotting. RAW264.7 cells and bone marrow mesenchymal stem cells (BMSCs) were cultured with USC-EVs to verify osteoclast differentiation and osteoblast formation, respectively, in vitro. The effects of USC-EVs were investigated on a UHMWPE particle-induced murine calvarial osteolysis model by assessing bone mass, the inflammatory reaction, and osteoblast and osteoclast formation. Results USCs differentiated into osteogenic, adipogenic and chondrogenic cells in vitro and were positive for CD44, CD73, CD29 and CD90 but negative for CD34 and CD45. USC-EVs exhibited a cup-like morphology with a double-layered membrane structure and were positive for CD63 and TSG101 and negative for calnexin. In vitro, USC-EVs promoted the osteogenic differentiation of BMSCs and reduced proinflammatory factor production and osteoclastic activity in RAW264.7 cells. In vivo, local injection of USC-EVs around the central sites of the calvaria decreased inflammatory cytokine generation and osteolysis compared with the control groups and significantly increased bone formation. Conclusion Based on our findings, USC-EVs prevent UHMWPE particle-induced osteolysis by decreasing inflammation, suppressing bone resorption and promoting bone formation.
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Affiliation(s)
- Hui Li
- Department of Orthopedics, Xiangya Hospital, Central South University, Changsha, Hunan, People's Republic of China.,Hunan Engineering Research Center of Biomedical Metal and Ceramic Implants, Xiangya Hospital, Central South University, Changsha, Hunan, People's Republic of China
| | - Xiao-Lei Fan
- Department of Orthopedics, Xiangya Hospital, Central South University, Changsha, Hunan, People's Republic of China.,Hunan Engineering Research Center of Biomedical Metal and Ceramic Implants, Xiangya Hospital, Central South University, Changsha, Hunan, People's Republic of China
| | - Yi-Nan Wang
- Department of Orthopedics, Xiangya Hospital, Central South University, Changsha, Hunan, People's Republic of China.,Hunan Engineering Research Center of Biomedical Metal and Ceramic Implants, Xiangya Hospital, Central South University, Changsha, Hunan, People's Republic of China
| | - Wei Lu
- Department of Orthopedics, Xiangya Hospital, Central South University, Changsha, Hunan, People's Republic of China.,Hunan Engineering Research Center of Biomedical Metal and Ceramic Implants, Xiangya Hospital, Central South University, Changsha, Hunan, People's Republic of China
| | - Haoyi Wang
- Department of Orthopedics, Xiangya Hospital, Central South University, Changsha, Hunan, People's Republic of China.,Hunan Engineering Research Center of Biomedical Metal and Ceramic Implants, Xiangya Hospital, Central South University, Changsha, Hunan, People's Republic of China
| | - Runzhi Liao
- Department of Orthopedics, Xiangya Hospital, Central South University, Changsha, Hunan, People's Republic of China.,Hunan Engineering Research Center of Biomedical Metal and Ceramic Implants, Xiangya Hospital, Central South University, Changsha, Hunan, People's Republic of China
| | - Min Zeng
- Department of Orthopedics, Xiangya Hospital, Central South University, Changsha, Hunan, People's Republic of China.,Hunan Engineering Research Center of Biomedical Metal and Ceramic Implants, Xiangya Hospital, Central South University, Changsha, Hunan, People's Republic of China
| | - Jun-Xiao Yang
- Department of Orthopedics, Xiangya Hospital, Central South University, Changsha, Hunan, People's Republic of China.,Hunan Engineering Research Center of Biomedical Metal and Ceramic Implants, Xiangya Hospital, Central South University, Changsha, Hunan, People's Republic of China
| | - Yihe Hu
- Department of Orthopedics, Xiangya Hospital, Central South University, Changsha, Hunan, People's Republic of China.,Hunan Engineering Research Center of Biomedical Metal and Ceramic Implants, Xiangya Hospital, Central South University, Changsha, Hunan, People's Republic of China
| | - Jie Xie
- Department of Orthopedics, Xiangya Hospital, Central South University, Changsha, Hunan, People's Republic of China.,Hunan Engineering Research Center of Biomedical Metal and Ceramic Implants, Xiangya Hospital, Central South University, Changsha, Hunan, People's Republic of China
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Shi T, Cheung M. Urine-derived induced pluripotent/neural stem cells for modeling neurological diseases. Cell Biosci 2021; 11:85. [PMID: 33985584 PMCID: PMC8117626 DOI: 10.1186/s13578-021-00594-5] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2020] [Accepted: 04/29/2021] [Indexed: 01/05/2023] Open
Abstract
Neurological diseases are mainly modeled using rodents through gene editing, surgery or injury approaches. However, differences between humans and rodents in terms of genetics, neural development, and physiology pose limitations on studying disease pathogenesis in rodent models for neuroscience research. In the past decade, the generation of induced pluripotent stem cells (iPSCs) and induced neural stem cells (iNSCs) by reprogramming somatic cells offers a powerful alternative for modeling neurological diseases and for testing regenerative medicines. Among the different somatic cell types, urine-derived stem cells (USCs) are an ideal cell source for iPSC and iNSC reprogramming, as USCs are highly proliferative, multipotent, epithelial in nature, and easier to reprogram than skin fibroblasts. In addition, the use of USCs represents a simple, low-cost and non-invasive procedure for generating iPSCs/iNSCs. This review describes the cellular and molecular properties of USCs, their differentiation potency, different reprogramming methods for the generation of iPSCs/iNSCs, and their potential applications in modeling neurological diseases.
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Affiliation(s)
- Tianyuan Shi
- School of Biomedical Sciences, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China
| | - Martin Cheung
- School of Biomedical Sciences, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China.
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18
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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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Bahir B, S. Choudhery M, Hussain I. Hypoxic Preconditioning as a Strategy to Maintain the Regenerative Potential of Mesenchymal Stem Cells. Regen Med 2020. [DOI: 10.5772/intechopen.93217] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/08/2022] Open
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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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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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Xing F, Li L, Sun J, Liu G, Duan X, Chen J, Liu M, Long Y, Xiang Z. Surface mineralized biphasic calcium phosphate ceramics loaded with urine-derived stem cells are effective in bone regeneration. J Orthop Surg Res 2019; 14:419. [PMID: 31818319 PMCID: PMC6902489 DOI: 10.1186/s13018-019-1500-7] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/04/2019] [Accepted: 11/27/2019] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND Segmental bone defects caused by trauma, tumors, or infection are a serious challenge for orthopedists in the world. Recent developments in tissue engineering have provided a new treatment for segmental bone defects. Urine-derived stem cells (USCs) can be obtained noninvasively and might be a new kind of seed cells used in bone tissue regeneration. Therefore, the first aim of the present study was to investigate the biological characteristics of USCs. The second aim of the present study was to study the osteogenic effect of surface mineralized biphasic calcium phosphate ceramics (BCPs) loaded with USCs in vitro and in vivo. METHODS We isolated USCs from the urine of healthy adult donors and evaluated the biological characteristics of USCs in vitro. We mineralized the surface of BCPs by simulated body fluid (SBF). Cell adhesion and proliferation of USCs on the surface mineralized BCPs were evaluated. Osteogenic proteins and genes of USCs on the surface mineralized BCPs were texted by enzyme-linked immunosorbent assay (ELISA) and real-time polymerase chain reaction (RT-PCR) assay. Critical-sized segmental bone defects model in New Zealand white rabbits were established and randomly divided into 4 groups (surface mineralized BCPs loaded with USCs, BCPs loaded with USCs, surface mineralized BCPs, and BCPs) based on the implant they received. The therapeutic efficacy of the scaffolds in a large bone defect at post-implantation was evaluated by imaging and histological examination. RESULTS USCs isolated in our study expressed stem cell-specific phenotypes and had a stable proliferative capacity and multipotential differentiation capability. Surface mineralized BCPs promoted osteogenic proteins and genes expression of USCs without affecting the proliferation of USCs. After 10 weeks, the amount of new bone formation was the highest in the group of surface mineralized BCPs loaded with USCs. CONCLUSION USCs, from non-invasive sources, have good application prospects in the field of bone tissue engineering. Surface mineralized BCPs can significantly enhance osteogenic potential of USCs without changing biological characteristics of BCPs. Surface mineralized BCPs loaded with USCs are effective in repairing of critical-sized segmental bone defects in rabbits.
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Affiliation(s)
- Fei Xing
- Department of Orthopaedics, West China Hospital, Sichuan University, No. 37 Guoxue Lane, Chengdu, 610041 Sichuan People’s Republic of China
| | - Lang Li
- Department of Pediatric Surgery, West China Hospital, Sichuan University, No. 37 Guoxue Lane, Chengdu, 610041 Sichuan People’s Republic of China
| | - Jiachen Sun
- Department of Orthopaedics, West China Hospital, Sichuan University, No. 37 Guoxue Lane, Chengdu, 610041 Sichuan People’s Republic of China
| | - Guoming Liu
- Department of Orthopaedics, West China Hospital, Sichuan University, No. 37 Guoxue Lane, Chengdu, 610041 Sichuan People’s Republic of China
| | - Xin Duan
- Department of Orthopaedics, West China Hospital, Sichuan University, No. 37 Guoxue Lane, Chengdu, 610041 Sichuan People’s Republic of China
| | - Jialei Chen
- Department of Orthopaedics, West China Hospital, Sichuan University, No. 37 Guoxue Lane, Chengdu, 610041 Sichuan People’s Republic of China
| | - Ming Liu
- Department of Orthopaedics, West China Hospital, Sichuan University, No. 37 Guoxue Lane, Chengdu, 610041 Sichuan People’s Republic of China
| | - Ye Long
- Department of Orthopaedics, West China Hospital, Sichuan University, No. 37 Guoxue Lane, Chengdu, 610041 Sichuan People’s Republic of China
| | - Zhou Xiang
- Department of Orthopaedics, West China Hospital, Sichuan University, No. 37 Guoxue Lane, Chengdu, 610041 Sichuan People’s Republic of China
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Sun X, Zheng W, Qian C, Wu Q, Hao Y, Lu G. Focal adhesion kinase promotes BMP2-induced osteogenic differentiation of human urinary stem cells via AMPK and Wnt signaling pathways. J Cell Physiol 2019; 235:4954-4964. [PMID: 31663128 DOI: 10.1002/jcp.29374] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/03/2019] [Accepted: 09/27/2019] [Indexed: 12/18/2022]
Abstract
Human urine-derived stem cells (hUSCs) serve as favorable candidates for bone transplants due to their efficient proliferative and multipotent differentiation abilities, as well as the capacity to secrete a variety of vasoactive agents to facilitate tissue engineering. The present study aimed to explore the role of focal adhesion kinase (FAK) in bone morphogenetic protein 2 (BMP2)-induced osteogenic differentiation of hUSCs and to investigate the underlying mechanism. The degree of osteogenic differentiation and the correlated signals, following BMP2 overexpression and siRNA-mediated silencing of FAK, were determined in vitro. Moreover, hUSCs induced bone formation in a rat model with cranial defects, in vivo. Our findings revealed that alkaline phosphatase production, calcium deposits, osteocalcin and osteopontin expression, and bone formation were upregulated in vitro and in vivo following BMP2-induced osteogenic differentiation, and AMPK and Wnt signaling pathway activation by FAK could effectively regulate BMP2-enhanced osteogenic differentiation of hUSCs. Taken together, these findings indicated that FAK could mediate BMP2-enhanced osteogenic differentiation of hUSCs through activating adenosine 5'-monophosphate-activated protein kinase and Wnt signaling pathways.
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Affiliation(s)
- Xingwei Sun
- Department of Intervention, The Second Affiliated Hospital of Soochow University, Suzhou, China
| | - Weiwei Zheng
- Department of Orthopaedics, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou, China
| | - Chen Qian
- Department of Orthopaedics, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou, China
| | - Qin Wu
- Department of Ultrasound, The Affiliated Suzhou Science & Technology Town Hospital of Nanjing Medical University, Suzhou, China
| | - Yuefeng Hao
- Department of Orthopaedics, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou, China
| | - Guohai Lu
- Department of Orthopaedics, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou, China
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Xing F, Liu G, Duan X, Xiang Z. [The application of urine derived stem cells in regeneration of musculoskeletal system]. ZHONGGUO XIU FU CHONG JIAN WAI KE ZA ZHI = ZHONGGUO XIUFU CHONGJIAN WAIKE ZAZHI = CHINESE JOURNAL OF REPARATIVE AND RECONSTRUCTIVE SURGERY 2018; 32:1477-1482. [PMID: 30417628 PMCID: PMC8414118 DOI: 10.7507/1002-1892.201804024] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Subscribe] [Scholar Register] [Received: 04/08/2018] [Revised: 10/13/2018] [Indexed: 02/05/2023]
Abstract
Objective To review the application of urine derived stem cells (USCs) in regeneration of musculoskeletal system. Methods The original literature about USCs in the regeneration of musculoskeletal system was extensively reviewed and analyzed. Results The source of USCs is noninvasive and extensive. USCs express MSCs surface markers with stable proliferative and multi-directional differentiation capabilities, and are widely used in bone, skin, nerve, and other skeletal and muscle system regeneration fields and show a certain repair capacity. Conclusion USCs from non-invasive sources have a wide application prospect in the regeneration of musculoskeletal system, but the definite biological mechanism of its repair needs further study.
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Affiliation(s)
- Fei Xing
- Department of Orthopedics, West China Hospital, Sichuan University, Chengdu Sichuan, 610041, P.R.China
| | - Guoming Liu
- Department of Orthopedics, West China Hospital, Sichuan University, Chengdu Sichuan, 610041, P.R.China
| | - Xin Duan
- Department of Orthopedics, West China Hospital, Sichuan University, Chengdu Sichuan, 610041, P.R.China
| | - Zhou Xiang
- Department of Orthopedics, West China Hospital, Sichuan University, Chengdu Sichuan, 610041,
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Chen H, Li J, Yan H. The transplantation of human urine stem cells combined with chondroitinase ABC promotes brain-derived neurotrophic factor and nerve growth factor following spinal cord injury in rats. INTERNATIONAL JOURNAL OF CLINICAL AND EXPERIMENTAL PATHOLOGY 2018; 11:3858-3866. [PMID: 31949773 PMCID: PMC6962799] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Subscribe] [Scholar Register] [Received: 04/05/2018] [Accepted: 06/04/2018] [Indexed: 06/10/2023]
Abstract
Cells based on therapies are currently gaining momentum in neural tissue engineering to treat spinal cord injury (SCI). The present study aimed to evaluate the effects of the concomitant use of human urine stem cells (hUSCs) and chondroitinase ABC (ChABC) on functional improvement and to explore the expressions of brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF). The SCI model was induced by a falling heavy object. hUSCs were cultured and transplanted into the impaired spinal cord with ChABC administration. The Basso, Beattie and Bresnahan (BBB) scores were valued, and real time PCR, immunofluorescence and Western blot were used to detect the expression of BDNF and NGF. We found that rats receiving both hUSCs and ChABC treatment demonstrated the best functional recovery. In addition, the mRNA and protein expressions of the BDNF and NGF expressions were found to be effectively higher in the combined treatment group than these in the other groups. In conclusion, hUSCs transplantation combined with ChABC administration promotes motor functional recovery in SCI rats, which may be associated with BDNF and NGF regulation.
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Affiliation(s)
- Hemu Chen
- Department of Rehabilitation Medicine, The First Affiliated Hospital of Anhui Medical University China
| | - Jian Li
- Department of Rehabilitation Medicine, The First Affiliated Hospital of Anhui Medical University China
| | - Han Yan
- Department of Rehabilitation Medicine, The First Affiliated Hospital of Anhui Medical University China
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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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Human Urine-Derived Stem Cells: Potential for Cell-Based Therapy of Cartilage Defects. Stem Cells Int 2018; 2018:4686259. [PMID: 29765413 PMCID: PMC5932456 DOI: 10.1155/2018/4686259] [Citation(s) in RCA: 35] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2017] [Revised: 02/25/2018] [Accepted: 03/19/2018] [Indexed: 02/05/2023] Open
Abstract
Stem cell therapy is considered an optimistic approach to replace current treatments for cartilage defects. Recently, human urine-derived stem cells (hUSCs), which are isolated from the urine, are studied as a promising candidate for many tissue engineering therapies due to their multipotency and sufficient proliferation activities. However, it has not yet been reported whether hUSCs can be employed in cartilage defects. In this study, we revealed that induced hUSCs expressed chondrogenic-related proteins, including aggrecan and collagen II, and their gene expression levels were upregulated in vitro. Moreover, we combined hUSCs with hyaluronic acid (HA) and injected hUSCs-HA into a rabbit knee joint with cartilage defect. Twelve weeks after the injection, the histologic analyses (HE, toluidine blue, and Masson trichrome staining), immunohistochemistry (aggrecan and collagen II), and histologic grade of the sample indicated that hUSCs-HA could stimulate much more neocartilage formation compared with hUSCs alone, pure HA, and saline, which only induced the modest cartilage regeneration. In this study, we demonstrated that hUSCs could be a potential cell source for stem cell therapies to treat cartilage-related defects in the future.
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