Direct Reprogramming of Human Bone Marrow Stromal Cells into Functional Renal Cells Using Cell-free Extracts
| Autor: | Evangelia Papadimou, Marina Morigi, Paraskevas Iatropoulos, Christodoulos Xinaris, Susanna Tomasoni, Valentina Benedetti, Lorena Longaretti, Cinzia Rota, Marta Todeschini, Paola Rizzo, Martino Introna, Maria Grazia de Simoni, Giuseppe Remuzzi, Michael S. Goligorsky, Ariela Benigni |
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| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: | |
| Zdroj: | Stem Cell Reports, Vol 4, Iss 4, Pp 685-698 (2015) |
| Druh dokumentu: | article |
| ISSN: | 2213-6711 82461589 |
| DOI: | 10.1016/j.stemcr.2015.02.002 |
| Popis: | 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. |
| Databáze: | Directory of Open Access Journals |
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