Human induced pluripotent stem cell-derived mesenchymal stem cells prevent adriamycin nephropathy in mice

Hao Jia Wu, Wai Han Yiu, Dickson W.L. Wong, Rui Xi Li, Loretta Y.Y. Chan, Joseph C.K. Leung, Yuelin Zhang, Qizhou Lian, Kar Neng Lai, Hung Fat Tse, Sydney C.W. Tang

Research output: Contribution to journalArticlepeer-review

7 Scopus citations

Abstract

Human induced pluripotent stem cell-derived mesenchymal stem cells (iPSMSCs) are emerging as attractive options for use in cell replacement therapy, but their effect in kidney diseases remains unknown. Here, we showed that intravenous injection of iPS-MSCs protect against renal function loss in both short-term and long-term models of adriamycin nephropathy (AN). In the short-term AN model, iPS-MSCs conferred a substantial anti-apoptotic effect on tubular cells, associated with a downregulation of Bax and Bax/Bcl2 ratio and an upregulation of survivin expression. In vitro, conditioned medium from iPS-MSCs (iPSMSC-CM) significantly limited albumin-induced tubular apoptosis and enhanced tubular proliferation, accompanied by a reduced expression of tubular Bax and an elevated expression of Bcl2 and survivin. Oxidative stress was markedly attenuated by iPS-MSCs both in AN mice and in protein-overloaded tubular cells. In the long-term AN model, repeated injections of iPS-MSCs significantly inhibited tubulointerstitial fibrosis and reduced intrarenal deposition of collagen I, collagen IV and aSMA. Modulation of the hedgehog signaling pathway contributed to the anti-fibrotic effect of iPS-MSCs in chronic AN. Finally, we detected that most of the infused iPS-MSCs were entrapped in the lungs. In conclusion, our data support a beneficial role of iPS-MSCs in both acute and chronic AN.

Original languageEnglish
Pages (from-to)103640-103656
Number of pages17
JournalOncotarget
Volume8
Issue number61
DOIs
StatePublished - 2017

Keywords

  • Adriamycin nephropathy
  • Apoptosis
  • Fibrosis
  • Induced pluripotent stem cells
  • Mesenchymal stem cells

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