title: Transplantation of induced pluripotent stem cell-derived renal stem cells improved acute kidney injury.
abstract: BACKGROUND
  Acute kidney injury (AKI) is a severe disease with high morbidity and mortality. Methods that promote repair of the injured kidney have been extensively investigated. Cell-based therapy with mesenchymal stem cells or renal progenitor cells (RPCs) resident in the kidney has appeared to be an effective strategy for the treatment of AKI. Embryonic stem cells or induced pluripotent stem cells (iPSCs) are also utilized for AKI recovery. However, the therapeutic effect of iPSC-derived RPCs for AKI has yet to be determined.
  
  
  METHODS
  In this study, we induced iPSCs differentiation into RPCs using a nephrogenic cocktail of factors combined with the renal epithelial cell growth medium. We then established the rat ischemia-reperfusion injury (IR) model and transplanted the iPSC-derived RPCs into the injured rats in combination with the hydrogel. Next, we examined the renal function-related markers and renal histology to assess the therapeutic effect of the injected cells. Moreover, we investigated the mechanism by which iPSC-derived RPCs affect AKI caused by IR.
  
  
  RESULTS
  We showed that the differentiation efficiency of iPSCs to RPCs increased when cultured with renal epithelial cell growth medium after stimulation with a nephrogenic cocktail of factors. The transplantation of iPSC-derived RPCs decreased the levels of biomarkers indicative of renal injury and attenuated the necrosis and apoptosis of renal tissues, but resulted in the up-regulation of renal tubules formation, cell proliferation, and the expression of pro-renal factors.
  
  
  CONCLUSIONS
  Our results revealed that iPSC-derived RPCs can protect AKI rat from renal function impairment and severe tubular injury by up-regulating the renal tubules formation, promoting cell proliferation, reducing apoptosis, and regulating the microenvironment in the injured kidney.
authors: Institute of Microsurgery on Extremities, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, 200233 China.
authors: Qing
authors: Q
authors: Li
authors: Department Nephrology and Rheumatology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, 200233 China.|Department of Integration of Traditional Chinese and Western Medicine, The First Affiliated Hospital of Soochow University, Suzhou, 215006 China.
authors: Shou-Fu
authors: SF
authors: Tian
authors: Department of Neurosurgery, Shandong Jining No. 1 People's Hospital, Jining, 272011 China.
authors: Ye
authors: Y
authors: Guo
authors: Institute of Microsurgery on Extremities, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, 200233 China.
authors: Xin
authors: X
authors: Niu
authors: Institute of Microsurgery on Extremities, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, 200233 China.
authors: Bin
authors: B
authors: Hu
authors: Institute of Microsurgery on Extremities, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, 200233 China.
authors: Shang-Chun
authors: SC
authors: Guo
authors: Department Nephrology and Rheumatology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, 200233 China.
authors: Nian-Song
authors: NS
authors: Wang
authors: Institute of Microsurgery on Extremities, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, 200233 China.
authors: Yang
authors: Y
authors: Wang
keywords: Acute kidney injury; Hydrogel; Renal ischemia–reperfusion injury; iPSC-derived RPCs