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Biological characteristics of human-urine-derived stem cells: potential for cell-based therapy in neurology.

ABSTRACT: Stem cells in human urine have gained attention in recent years; however, urine-derived stem cells (USCs) are far from being well elucidated. In this study, we compared the biological characteristics of USCs with adipose-derived stem cells (ASCs) and investigated whether USCs could serve as a potential cell source for neural tissue engineering. USCs were isolated from voided urine with a modified culture medium. Through a series of experiments, we examined the growth rate, surface antigens, and differentiation potential of USCs, and compared them with ASCs. USCs showed robust proliferation ability. After serial propagation, USCs retained normal karyotypes. Cell surface antigen expression of USCs was similar to ASCs. With lineage-specific induction factors, USCs could differentiate toward the osteogenic, chondrogenic, adipogenic, and neurogenic lineages. To assess the ability of USCs to survive, differentiate, and migrate, they were seeded onto hydrogel scaffold and transplanted into rat brain. The results showed that USCs were able to survive in the lesion site, migrate to other areas, and express proteins that were associated with neural phenotypes. The results of our study demonstrate that USCs possess similar biological characteristics with ASCs and have multilineage differentiation potential. Moreover USCs can differentiate to neuron-like cells in rat brain. The present study shows that USCs are a promising cell source for tissue engineering and regenerative medicine.

SUBMITTER: Guan JJ

PROVIDER: S-EPMC4086681 | biostudies-literature | 2014 Jul

REPOSITORIES: biostudies-literature

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Biological characteristics of human-urine-derived stem cells: potential for cell-based therapy in neurology.

Guan Jun-Jie JJ Niu Xin X Gong Fei-Xiang FX Hu Bin B Guo Shang-Chun SC Lou Yuan-Lei YL Zhang Chang-Qing CQ Deng Zhi-Feng ZF Wang Yang Y

Tissue engineering. Part A 20140519 13-14

Stem cells in human urine have gained attention in recent years; however, urine-derived stem cells (USCs) are far from being well elucidated. In this study, we compared the biological characteristics of USCs with adipose-derived stem cells (ASCs) and investigated whether USCs could serve as a potential cell source for neural tissue engineering. USCs were isolated from voided urine with a modified culture medium. Through a series of experiments, we examined the growth rate, surface antigens, and ...[more]

PMID: 24387670

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Project description:BackgroundStem cells are the main choice for seed cells in tissue engineering, but using most traditional stem cells requires invasive and complicated procedures. Human urine-derived stem cells (hUSCs) are an alternative stem cell source with the advantages of being isolated noninvasively and repetitively from the same individual. The aim of this study was to compare chondrogenesis-related biological behaviors between hUSCs and human bone marrow mesenchymal stem cells (hBMSCs) from the same individual.MethodshUSCs and hBMSCs were isolated from six patients who underwent iliac bone grafting. Cell morphology, proliferation, colony-forming, migration, and multidifferentiation analyses were performed in vitro. Then, acellular cartilage extracellular matrix (ACM) scaffolds were fabricated for in vivo implantation. The comparisons of cell viability, morphology, proliferation, and chondrogenesis between hUSCs and hBMSCs cultured on scaffolds were performed before implantation. The scaffolds loaded with hUSCs or hBMSCs were implanted into a rabbit knee model to repair cartilage defects. Magnetic resonance imaging (MRI) and micro-computed tomography (μCT) Analyses, inflammation and toxicity assays, gross observation, and histological evaluation were performed to evaluate the cartilage repair effects.ResultsIn in vitro experiments, hUSCs had better capacity for proliferation, colony-forming, and migration compared to hBMSCs in the same passage, while hBMSCs had greater osteogenic, adipogenic, and chondrogenic abilities compared to hUSCs in the same passage. Both hUSCs and hBMSCs at passage 3 had the strongest potential for proliferation, colony-forming, and multilineage differentiation compared to cells in other passages. The ACM scaffolds loaded with hUSCs or hBMSCs both significantly promoted the repair of cartilage defects in the rabbit knee model at 12 weeks' postimplantation, and the new tissue was mainly hyaline cartilage. However, there was no significant difference in cartilage repair effects between hUSCs and hBMSCs.ConclusionsIn in vitro experiments, hUSCs presented better capacity for proliferation, while hBMSCs had greater chondrogenic ability. However, hUSCs and hBMSCs had similar cartilage repair effects in vivo. Results indicated that hUSCs can be a stem cell alternative for cartilage regeneration and provide a powerful platform for cartilage tissue engineering and clinical transformation.

Project description:BackgroundAutologous urothelial cells are often obtained via bladder biopsy to generate the bio-engineered urethra or bladder, while urine-derived stem cells (USC) can be obtained by a non-invasive approach. The objective of this study is to develop an optimal strategy for urothelium with permeability barrier properties using human USC which could be used for tissue repair in the urinary tract system.MethodsUSC were harvested from six healthy adult individuals. To optimize urothelial differentiation, five different differentiation methods were studied. The induced cells were assessed for gene and protein expression markers of urothelial cells via RT-PCR, Western blotting, and immunofluorescent staining. Barrier function and ultrastructure of the tight junction were assessed with permeability assays and transmission electron microscopy (TEM). Induced cells were both cultured on trans-well membranes and small intestinal submucosa, then investigated under histology analysis.ResultsDifferentiated USC expressed significantly higher levels of urothelial-specific transcripts and proteins (Uroplakin III and Ia), epithelial cell markers (CK20 and AE1/AE3), and tight junction markers (ZO-1, ZO-2, E-cadherin, and Cingulin) in a time-dependent manner, compared to non-induced USC. In vitro assays using fluorescent dye demonstrated a significant reduction in permeability of differentiated USC. In addition, transmission electron microscopy confirmed appropriate ultrastructure of urothelium differentiated from USC, including tight junction formation between neighboring cells, which was similar to positive controls. Furthermore, multilayered urothelial tissues formed 2 weeks after USC were differentiated on intestine submucosal matrix.ConclusionThe present study illustrates an optimal strategy for the generation of differentiated urothelium from stem cells isolated from the urine. The induced urothelium is phenotypically and functionally like native urothelium and has proposed uses in in vivo urological tissue repair or in vitro urethra or bladder modeling.

Project description:Background: Periprosthetic osteolysis is the primary reason for arthroplasty failure after total joint replacement because of the generation of wear particles and subsequent bone erosion around the prosthesis, which leads to aseptic loosening. Periprosthetic osteolysis is often treated with revision surgery because of the lack of effective therapeutic agents. As key messengers of intercellular interactions, exosomes can be independently used as therapeutic agents to promote tissue repair and regeneration. In this study, we fabricated poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) that carry exosomes derived from human urine stem cells (USC-Exos) and explored their effects on polyethylene-induced osteolysis. Methods: USCs were identified by multipotent differentiation and flow cytometry analyses. USC-Exos were isolated and identified by transmission electron microscopy (TEM), dynamic light scattering (DLS), and western blotting. PLGA microspheres containing USC-Exos were fabricated to synthesize NPs using the mechanical double-emulsion method. The obtained NPs were characterized in terms of stability, toxicity, exosome release, and cell uptake. Then, these NPs were implanted into the murine air pouch model, and their effects on polyethylene-induced osteolysis were evaluated by microcomputed tomography (micro-CT) and histological analyses. Results: The average NP diameter was ~282 ± 0.4 nm, and the zeta potential was -2.02 ± 0.03 mV. After long-term storage at room temperature and 4°C, the NP solution was stable without significant coaggregation. In vitro release profiles indicated sustained release of exosomes for 12 days. In vivo, injection of NPs into the murine air pouch caused less osteolysis than that of USC-Exos, and NPs significantly reduced bone absorption, as indicated by histology and micro-CT scanning. Conclusion: Our findings suggest that USC-Exo-based PLGA NPs can prevent particulate polyethylene-induced osteolysis and bone loss.

Dataset Information

Biological characteristics of human-urine-derived stem cells: potential for cell-based therapy in neurology.

Publications

Biological characteristics of human-urine-derived stem cells: potential for cell-based therapy in neurology.

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