Direct Reprogramming of Human Bone Marrow Stromal Cells into Functional Renal Cells Using Cell-free Extracts

作者：Papadimou Evangelia^*; Morigi Marina; Iatropoulos Paraskevas; Xinaris Christodoulos; Tomasoni Susanna; Benedetti Valentina; Longaretti Lorena; Rota Cinzia; Todeschini Marta; Rizzo Paola; Introna Martino; de Simoni Maria Grazia; Remuzzi Giuseppe; Goligorsky Michael S; Benigni Ariela

来源：Stem Cell Reports, 2015, 4(4): 685-698.

DOI：10.1016/j.stemcr.2015.02.002

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.

• 出版日期2015-4-14