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