Human induced pluripotent stem cell-derived mesenchymal stem cells prevent adriamycin nephropathy in mice
Metrics: PDF 1481 views | HTML 2483 views | ?
Hao Jia Wu1, Wai Han Yiu1, Dickson W.L. Wong1, Rui Xi Li2, Loretta Y.Y. Chan1, Joseph C.K. Leung1, Yuelin Zhang3, Qizhou Lian3,4, Kar Neng Lai1, Hung Fat Tse3 and Sydney C.W. Tang1
1Nephrology Division, Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Pok Fu Lam, Hong Kong
2Institute of Laboratory Medicine, Guangdong Medical University, Dongguan, China
3Cardiology Division, Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Pok Fu Lam, Hong Kong
4Department of Ophthalmology, The University of Hong Kong, Queen Mary Hospital, Pok Fu Lam, Hong Kong
Sydney C.W. Tang, email: [email protected]
Keywords: induced pluripotent stem cells; mesenchymal stem cells; adriamycin nephropathy; apoptosis; fibrosis
Received: March 06, 2017 Accepted: September 21, 2017 Published: October 10, 2017
Human induced pluripotent stem cell-derived mesenchymal stem cells (iPS-MSCs) 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 αSMA. 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.
All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 4.0 License.