Journal
STEM CELL REPORTS
Volume 4, Issue 4, Pages 685-698Publisher
CELL PRESS
DOI: 10.1016/j.stemcr.2015.02.002
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Funding
- Fondazione Cariplo [2011-1642]
- European Commission [HEALTH-FP-2012-305436]
- NIH [DK54602, DK052783, DK45462]
- Westchester Artificial Kidney Foundation
- Fondazione Aiuti per la Ricerca sulle Malattie Rare (ARMR), Bergamo, Italy
- NICHD
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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 up-regulation 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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