Potency of Human Urine-Derived Stem Cells for Renal Lineage Differentiation

Kidney is one of the most difficult organs for regeneration. Several attempts have been performed to regenerate renal tissue using stem cells, the results were not satisfactory. Urine is major product of kidney and contains cells from renal components. Moreover, urine-derived stem cells (USCs) can be easily obtained without any health risks throughout a patient's entire life. Here, we evaluated the utility of USCs for renal tissue regeneration. In this study, the ability of USCs to differentiate into renal lineage cells was compared with that of adipose tissue-derived stem cells (ADSCs) and amniotic fluid-derived stem cells (AFSCs), with respect to surface antigen expression, morphology, immunocytochemistry, renal lineage gene expression, secreted factors, immunomodulatory marker expression, in vivo safety, and renal differentiation potency. Undifferentiated USCs were positive for CD44 and CD73, negative for CD34 and CD45, and formed aggregates after 3 weeks of renal differentiation. Undifferentiated USCs showed high SSEA4 expression, while renal-differentiated cells expressed PAX2, WT1, and CADHERIN 6. In the stem/renal lineageassociated gene analysis, OCT4, SSEA4, and CD117 were significantly downregulated over time, while PAX2, LIM1, PDGFRA, E-CADHERIN, CD24, ACTB, AQP1, OCLN, and NPHS1 were gradually upregulated. In the in vivo safety evaluation, renal-differentiated USCs did not show abnormal histology. These findings demonstrated that USCs have a similar MSC potency, renal lineage-differentiation ability, immunomodulatory effects, and in vivo safety as ADSCs and AFSCs, and showed higher levels of growth factor secretion for paracrine effects. Therefore, urine and USCs can be one of good cell sources for kidney regeneration.

Characterization and differentiation into adipocytes of mesenchymal stem cells (MSCs) from human adipose tissue and amniotic fluid / 대한산부인과학회지

OBJECTIVE: Mesenchymal stem cells (MSCs) are potentially very useful for regenerative and reparative medicine as well as therapeutic possibilities. The aim of this study is to examine the ability of ADSCs and AFSCs to be phenotypically and functionally differentiated into adipocyte and to determine the appropriate stem cell source and conditions for efficient adipocyte regeneration. METHODS: Adipogenic differentiation was induced by culturing confluent ADSCs and AFSCs in adipogenic medium for 2~4 weeks. During the differentiation inducing period, we evaluated the successful adipogenesis by performing immunocytochemistry and RT-PCR to detect the lipid producibility and several adipogenic gene expressions including lipoprotein lipase (LPL), peroxisome proliferator-activated receptor gamma2 (PPAR gamma2) and adiponectin. RESULTS: ADSCs and AFSCs are expanded easily in vitro and exhibited a fibroblast-like morphology as previously known in MSCs from bone marrow and a commercial source. Flow cytometric analysis showed that ADSCs and AFSCs expressed several CD marker antigens similar to those observed on bone marrow-derived MSCs. Adipogenic induction of ADSCs and AFSCs resulted in the extended cell morphology, intracellular staining of an established lipid dye Oil Red O, and expression of adipocyte-specific genes. CONCLUSION: Both ADSCs and AFSCs successfully differentiate in vitro into adipogenic cells in the presence of the lineage-specific induction factors although ADSC showed the greater capability. Therefore, the results suggest that ADSCs and AFSCs may be an excellent choice for many future tissue engineering strategies and cell-based therapies.