title: MicroRNA-498 Inhibition Enhances the Differentiation of Human Adipose-Derived Mesenchymal Stem Cells into Podocyte-Like Cells.
abstract: 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.
authors.affiliation: 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 .
authors.forename: Lina
authors.initials: L
authors.lastname: Zhang
authors.affiliation: 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 .
authors.forename: Kanghua
authors.initials: K
authors.lastname: Li
authors.affiliation: 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 .
authors.forename: Xi
authors.initials: X
authors.lastname: Yan
authors.affiliation: 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 .
authors.forename: Xiaolei
authors.initials: X
authors.lastname: Liang
authors.affiliation: 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 .
authors.forename: Shihua
authors.initials: S
authors.lastname: Wang
authors.affiliation: 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 .
authors.forename: Qin
authors.initials: Q
authors.lastname: Han
authors.affiliation: 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 .|2 Peking Union Medical College Hospital , Beijing, People's Republic of China .
authors.forename: Robert Chunhua
authors.initials: RC
authors.lastname: Zhao
mesh_terms: D028341:Activins / Q000494:pharmacology; D000273:Adipose Tissue / Q000166:cytology; D000818:Animals; D055419:Bone Morphogenetic Protein 7 / Q000494:pharmacology; D002454:Cell Differentiation; D002478:Cells, Cultured; D006801:Humans; D007668:Kidney / Q000166:cytology / Q000502:physiology; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D035683:MicroRNAs / Q000037:antagonists & inhibitors*; D050199:Podocytes / Q000166:cytology* / Q000378:metabolism; D012038:Regeneration; D014212:Tretinoin / Q000494:pharmacology
chemical_list: D055419:Bone Morphogenetic Protein 7; C578093:MIRN498 microRNA, human; D035683:MicroRNAs; C422405:activin A; D028341:Activins; D014212:Tretinoin