Urine-derived stem cells: applications in skin, bone and articular cartilage repair.
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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.
Project description:BACKGROUND:The role of rabbit synovial fluid-derived mesenchymal stem cells (rbSF-MSCs) in cartilage defect repair remains undefined. This work evaluates the in vivo effects of rbSF-MSCs to repair knee articular cartilage defects in a rabbit model. METHODS:Cartilage defects were made in the patellar grooves of New Zealand white rabbits. The rbSF-MSCs were generated from the knee cavity by arthrocentesis. Passage 5 rbSF-MSCs were assayed by flow cytometry. The multipotency of rbSF-MSCs was confirmed after 3 weeks induction in vitro and the autologous rbSF-MSCs and predifferentiated rbSF-MSCs were injected into the synovial cavity. The intra-articular injection was performed once a week for 4 weeks. The animals were euthanized and the articular surfaces were subjected to macroscopic and histological evaluations at 8 and 12 weeks after the first intra-articular injection. RESULTS:Hyaline-like cartilage was detected in the defects treated with rbSF-MSCs, while fibrocartilage tissue formed in the defects treated with chondrocytes induced from rbSF-MSCs. CONCLUSIONS:Our results suggest that autologous undifferentiated rbSF-MSCs are favorable to articular cartilage regeneration in treating cartilage defects.
Project description:ObjectivesFunctions of mesenchymal stem/stromal cells (MSCs) are affected by patient-dependent factors such as age and health condition. To tackle this problem, we used the cellular reprogramming technique to epigenetically alter human MSCs derived from the synovial fluid of joints with osteoarthritis (OA) to explore the potential of reprogrammed MSCs for repairing articular cartilage.Materials and methodsMSCs isolated from the synovial fluid of three patients' OA knees (Pa-MSCs) were reprogrammed through overexpression of pluripotency factors and then induced for differentiation to establish reprogrammed MSC (Re-MSC) lines. We compared the in vitro growth characteristics, chondrogenesis for articular cartilage chondrocytes, and immunomodulatory capacity. We also evaluated the capability of Re-MSCs to repair articular cartilage damage in an animal model with spontaneous OA.ResultsOur results showed that Re-MSCs increased the in vitro proliferative capacity and improved chondrogenic differentiation toward articular cartilage-like chondrocyte phenotypes with increased THBS4 and SIX1 and decreased ALPL and COL10A1, compared to Pa-MSCs. In addition, Re-MSC-derived chondrocytes expressing elevated COL2A and COL2B were more mature than parental cell-derived ones. The enhancement in chondrogenesis of Re-MSC involves the upregulation of sonic hedgehog signaling. Moreover, Re-MSCs improved the repair of articular cartilage in an animal model of spontaneous OA.ConclusionsEpigenetic reprogramming promotes MSCs harvested from OA patients to increase phenotypic characteristics and gain robust functions. In addition, Re-MSCs acquire an enhanced potential for articular cartilage repair. Our study here demonstrates that the reprogramming strategy provides a potential solution to the challenge of variation in MSC quality.
Project description:BackgroundThe characteristics and therapeutic potential of subtypes of bone marrow mesenchymal stem cells (BMSCs) are largely unknown. Also, the application of subpopulations of BMSCs in cartilage regeneration remains poorly characterized. The aim of this study was to explore the regenerative capacity of CD146-positive subpopulations of BMSCs for repairing cartilage defects.MethodsCD146-positive BMSCs (CD146 + BMSCs) were sorted by self-developed CD146-specific lipid magnetic spheres (CD146-LMS). Cell surface markers, viability, and proliferation were evaluated in vitro. CD146 + BMSCs were subjected to in vitro chondrogenic induction and evaluated for chondrogenic properties by detecting mRNA and protein expression. The role of the CD146 subpopulation of BMSCs in cartilage damage repair was assessed by injecting CD146 + BMSCs complexed with sodium alginate gel in the joints of a mouse cartilage defect model.ResultsThe prepared CD146-LMS had an average particle size of 193.7 ± 5.24 nm, an average potential of 41.9 ± 6.21 mv, and a saturation magnetization intensity of 27.2 Am2/kg, which showed good stability and low cytotoxicity. The sorted CD146 + BMSCs highly expressed stem cell and pericyte markers with good cellular activity and cellular value-added capacity. Cartilage markers Sox9, Collagen II, and Aggrecan were expressed at both protein and mRNA levels in CD146 + BMSCs cells after chondrogenic induction in vitro. In a mouse cartilage injury model, CD146 + BMSCs showed better function in promoting the repair of articular cartilage injury.ConclusionThe prepared CD146-LMS was able to sort out CD146 + BMSCs efficiently, and the sorted subpopulation of CD146 + BMSCs had good chondrogenic differentiation potential, which could efficiently promote the repair of articular cartilage injury, suggesting that the sorted CD146 + BMSCs subpopulation is a promising seed cell for cartilage tissue engineering.
Project description:Purpose of researchThe potential for cartilage repair using articular cartilage derived chondroprogenitors has recently gained popularity due to promising results from in-vitro and in-vivo studies. Translation of results from in-vitro to a clinical setting requires a sufficient number of animal studies displaying significant positive outcomes. Thus, this systematic review comprehensively discusses the available literature (January 2000-March 2022) on animal models employing chondroprogenitors for cartilage regeneration, highlighting the results and limitations associated with their use.As per Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, a web-based search of PubMed and SCOPUS databases was performed for the following terminologies: "chondroprogenitors", "cartilage-progenitors", and "chondrogenic-progenitors", which yielded 528 studies. A total of 12 studies met the standardized inclusion criteria, which included chondroprogenitors derived from hyaline cartilage isolated using fibronectin adhesion assay (FAA) or migratory assay from explant cultures, further analyzing the role of chondroprogenitors using in-vivo animal models.Principal resultsAnalysis revealed that FAA chondroprogenitors demonstrated the ability to attenuate osteoarthritis, repair chondral defects and form stable cartilage in animal models. They displayed better outcomes than bone marrow-derived mesenchymal stem cells but were comparable to chondrocytes. Migratory chondroprogenitors also demonstrated superiority to BM-MSCs in terms of higher chondrogenesis and lower hypertrophy, although a direct comparison to FAA-CPs and other cell types is warranted.Major conclusionsChondroprogenitors exhibit superior properties for chondrogenic repair; however, limited data on animal studies necessitates further studies to optimize their use before clinical translation for neo-cartilage formation.
Project description:Articular cartilage defect is challenged by insufficient regenerative ability of cartilage. Catalpol (CA), the primary active component of Rehmanniae Radix, could exert protective effects against various diseases. However, the impact of CA on the treatment of articular cartilage injuries is still unclear. In this study, full-thickness articular cartilage defect was induced in a mouse model via surgery. The animals were intraperitoneally injected with CA for 4 or 8 weeks. According to the results of macroscopic observation, micro-computed tomography CT (μCT), histological and immunohistochemistry staining, CA treatment could promote mouse cartilage repair, resulting in cartilage regeneration, bone structure improvement and matrix anabolism. Specifically, an increase in the expression of CD90, the marker of mesenchymal stem cells (MSCs), in the cartilage was observed. In addition, we evaluated the migratory and chondrogenic effects of CA on MSCs. Different concentration of CA was added to C3H10 T1/2 cells. The results showed that CA enhanced cell migration and chondrogenesis without affecting proliferation. Collectively, our findings indicate that CA may be effective for the treatment of cartilage defects via stimulation of endogenous MSCs.
Project description:Objective Articular cartilage is an avascular tissue with limited ability of self-regeneration and the current clinical treatments have restricted capacity to restore damages induced by trauma or diseases. Therefore, new techniques are being tested for cartilage repair, using scaffolds and/or stem cells. Although type II collagen hydrogel, fibrin sealant, and adipose-derived stem cells (ASCs) represent suitable alternatives for cartilage formation, their combination has not yet been investigated in vivo for focal articular cartilage defects. We performed a simple experimental procedure using the combination of these 3 compounds on cartilage lesions of rabbit knees. Design The hydrogel was developed in house and was first tested in vitro for chondrogenic differentiation. Next, implants were performed in chondral defects with or without ASCs and the degree of regeneration was macroscopically and microscopically evaluated. Results Production of proteoglycans and the increased expression of collagen type II (COL2α1), aggrecan (ACAN), and sex-determining region Y-box 9 (SOX9) confirmed the chondrogenic character of ASCs in the hydrogel in vitro. Importantly, the addition of ASC induced a higher overall repair of the chondral lesions and a better cellular organization and collagen fiber alignment compared with the same treatment without ASCs. This regenerating tissue also presented the expression of cartilage glycosaminoglycan and type II collagen. Conclusions Our results indicate that the combination of the 3 compounds is effective for articular cartilage repair and may be of future clinical interest.
Project description: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.
Project description:Functional repair of articular cartilage defects is always a great challenge in joint surgery clinically. Tissue engineering strategies that combine autologous cell implantation with three-dimensional scaffolds have proven effective for repairing articular cartilage tissue. However, it faces the problem of cell sources and scaffold materials. Autologous chondrocytes and bone marrow are difficult to popularize clinically due to limited donor sources and low mononuclear cell (MNC) concentrations, respectively. The density gradient centrifugation method can increase the concentration of MNCs in fresh bone marrow by nearly a hundredfold and achieve immediate enrichment. In addition, acellular cartilage matrix (ACM), with good biocompatibility and a cartilage-specific microenvironment, is considered to be an ideal candidate scaffold for cartilage regeneration. In this study, hybrid pigs were used to establish articular cartilage defect models of different sizes to determine the feasibility and maximum scope of application of ACM-based biomimetic scaffolds combined with MNCs for inducing articular cartilage regeneration. Importantly, ACM-based biomimetic scaffolds instantly enriched MNCs could improve the repair effect of articular cartilage defects in situ, which established a new model of articular cartilage regeneration that could be applied immediately and suited for large-scale clinical promotion. The current study significantly improves the repair effect of articular cartilage defects, which provides scientific evidence and detailed insights for future clinical applications of ACM-based biomimetic scaffolds combined with MNCs.
Project description:Reconstruction of complex cartilage defects has remained a great challenge for tissue engineering due to the lack of stem cells and chronic inflammation within the joint. In this study, we have developed an injectable pig cartilage-derived decellularized extracellular matrix (dECM) hydrogels for the repair of cartilage defects, which has shown sound biocompatibility and immunomodulatory capacity both in vitro and in vivo. The dECM hydrogels can enhance the chondrogenic differentiation of human urine-derived stem cells (USCs). As shown by in vitro experiment, the USCs in the dECM hydrogels have survived, proliferated, and produced a mass of cartilage-specific extracellular matrix containing collagen II and aggrecan. And the USCs-laden dECM hydrogels have shown the capacity to promote the secretion of extracellular matrix, modulate the immune response and promote cartilage regeneration in the rat model for cartilage defect.
Project description:There has been increasing application of autologous costal chondral/osteochondral transplantation (ACCT/ACOT) and costa-derived chondrocyte implantation (ACCI) for articular cartilage repair over the past three decades. This review presents the major evidence on the properties of costal cartilage and bone and their qualifications as grafts for articular cartilage repair, the major clinical applications, and the risks and strategies for costal chondral/osteochondral graft(s) harvest. First, costal cartilage has many specific properties that help restore the articular surface. Costa, which can provide abundant cartilage and cylindrical corticocancellous bone, preserves permanent chondrocyte and is the largest source of hyaline cartilage. Second, in the past three decades, autologous costal cartilage-derived grafts, including cartilage, osteochondral graft(s), and chondrocyte, have expanded their indications in trauma and orthopaedic therapy from small to large joints, from the upper to lower limbs, and from non-weight-bearing to weight-bearing joints. Third, the rate of donor-site complications of ACCT or ACOT is low, acceptable, and controllable, and some skills and accumulated experience can help reduce the risks of ACCT and ACOT. Costal cartilage-derived autografting is a promising technique and could be an ideal option for articular chondral lesions with or without subchondral cysts. More high-quality clinical studies are urgently needed to help us further understand the clinical value of such technologies.