PMID- 26414643 OWN - NLM STAT- MEDLINE DCOM- 20161025 LR - 20181202 IS - 1557-8534 (Electronic) IS - 1547-3287 (Linking) VI - 24 IP - 24 DP - 2015 Dec 15 TI - MicroRNA-498 Inhibition Enhances the Differentiation of Human Adipose-Derived Mesenchymal Stem Cells into Podocyte-Like Cells. PG - 2841-52 LID - 10.1089/scd.2015.0027 [doi] AB - Podocyte depletion is a key event in the progression of end-stage kidney disease (ESKD) resulting in nephrotic proteinuria and renal failure, but the treatment options are limited to dialysis and renal transplantation. So there is an urgent need for renal regenerative therapies. Generation of podocytes from human stem cells is regarded as a promising therapeutic strategy to repair or regenerate the damaged kidneys; however, the reliable induction system remains a challenge. In this study, we established a two-stage induction protocol for podocyte generation from human adipose-derived mesenchymal stem cells (hAD-MSCs). We initially established a condition that induces hAD-MSCs toward intermediate mesoderm cells with activin A and high concentration of retinoic acid (RA). Subsequently, by using the combination of activin A and low concentration of RA and BMP7, we generated podocyte-like cells expressing multiple podocyte-specific markers and able to integrate into a developing nephron of embryonic kidney explant culture and ameliorate proteinuria and kidney injure in adriamycin-treated mice. Furthermore, we identified that miRNA-498 inhibitor has potential to improve the differentiation of hAD-MSCs into podocyte-like cells and established a robust induction protocol. Thereby, our study advocated an efficient method for the induction of kidney podocyte-like (iPod) cells from hAD-MSCs and provided an ideal candidate for regenerative therapies of the kidney. FAU - Zhang, Lina AU - Zhang L AD - 1 Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College , Beijing, People's Republic of China . FAU - Li, Kanghua AU - Li K AD - 1 Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College , Beijing, People's Republic of China . FAU - Yan, Xi AU - Yan X AD - 1 Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College , Beijing, People's Republic of China . FAU - Liang, Xiaolei AU - Liang X AD - 1 Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College , Beijing, People's Republic of China . FAU - Wang, Shihua AU - Wang S AD - 1 Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College , Beijing, People's Republic of China . FAU - Han, Qin AU - Han Q AD - 1 Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College , Beijing, People's Republic of China . FAU - Zhao, Robert Chunhua AU - Zhao RC AD - 1 Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College , Beijing, People's Republic of China . AD - 2 Peking Union Medical College Hospital , Beijing, People's Republic of China . LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20151026 PL - United States TA - Stem Cells Dev JT - Stem cells and development JID - 101197107 RN - 0 (Bone Morphogenetic Protein 7) RN - 0 (MIRN498 microRNA, human) RN - 0 (MicroRNAs) RN - 0 (activin A) RN - 104625-48-1 (Activins) RN - 5688UTC01R (Tretinoin) SB - IM MH - Activins/pharmacology MH - Adipose Tissue/cytology MH - Animals MH - Bone Morphogenetic Protein 7/pharmacology MH - *Cell Differentiation MH - Cells, Cultured MH - Humans MH - Kidney/cytology/physiology MH - Male MH - Mesenchymal Stem Cell Transplantation MH - Mesenchymal Stem Cells/*cytology/drug effects/metabolism MH - Mice MH - Mice, Inbred BALB C MH - MicroRNAs/*antagonists & inhibitors MH - Podocytes/*cytology/metabolism MH - Regeneration MH - Tretinoin/pharmacology EDAT- 2015/09/29 06:00 MHDA- 2016/10/26 06:00 CRDT- 2015/09/29 06:00 PHST- 2015/09/29 06:00 [entrez] PHST- 2015/09/29 06:00 [pubmed] PHST- 2016/10/26 06:00 [medline] AID - 10.1089/scd.2015.0027 [doi] PST - ppublish SO - Stem Cells Dev. 2015 Dec 15;24(24):2841-52. doi: 10.1089/scd.2015.0027. Epub 2015 Oct 26.