Direct reprogramming of human bone marrow stromal cells into functional renal cells using cell-free extracts

Stem Cell Reports
Evangelia PapadimouAriela Benigni

Abstract

The application of cell-based therapies in regenerative medicine is gaining recognition. Here, we show that human bone marrow stromal cells (BMSCs), also known as bone-marrow-derived mesenchymal cells, can be reprogrammed into renal proximal tubular-like epithelial cells using cell-free extracts. Streptolysin-O-permeabilized BMSCs exposed to HK2-cell extracts underwent morphological changes-formation of "domes" and tubule-like structures-and acquired epithelial functional properties such as transepithelial-resistance, albumin-binding, and uptake and specific markers E-cadherin and aquaporin-1. Transmission electron microscopy revealed the presence of brush border microvilli and tight intercellular contacts. RNA sequencing showed tubular epithelial transcript abundance and revealed the upregulation of components of the EGFR pathway. Reprogrammed BMSCs integrated into self-forming kidney tissue and formed tubular structures. Reprogrammed BMSCs infused in immunodeficient mice with cisplatin-induced acute kidney injury engrafted into proximal tubuli, reduced renal injury and improved function. Thus, reprogrammed BMSCs are a promising cell resource for future cell therapy.

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Citations

Jul 15, 2015·Expert Opinion on Biological Therapy·Elena LazzeriLaura Lasagni
Dec 22, 2015·Pediatric Nephrology : Journal of the International Pediatric Nephrology Association·Maria Giovanna Francipane, Eric Lagasse
Jul 15, 2015·Cell Transplantation·Maria Giovanna Francipane, Eric Lagasse
Jan 21, 2016·World Journal of Nephrology·Etsu SuzukiHiroaki Nishimatsu
Sep 20, 2018·Advanced Healthcare Materials·Cécile LegallaisDimitrios Stamatialis
Mar 16, 2017·Stem Cells Translational Medicine·Kei MatsumotoMichael S Goligorsky
Apr 14, 2020·Proceedings of the Japan Academy. Series B, Physical and Biological Sciences·Kenichi Horisawa, Atsushi Suzuki
Jun 1, 2017·Cell and Tissue Research·Michael M KaminskiSoeren S Lienkamp
Sep 22, 2019·Journal of the American Society of Nephrology : JASN·Michael S Goligorsky

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Methods Mentioned

BETA
transmission electron microscopy
flow cytometry
FACS
transfection
scanning electron microscopy
light microscopy
RNA-Seq
transmission

Software Mentioned

UCSC Genome Browser
GraphiteWeb
FeatureCounter
TorrentSuite
HTSeq
RobiNA
ToppFun
edgeR

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