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

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

Research output: Contribution to journalArticlepeer-review

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, albuminbinding, 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.

Original languageEnglish
Pages (from-to)685-698
Number of pages14
JournalStem Cell Reports
Volume4
Issue number4
DOIs
Publication statusPublished - 2015

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Developmental Biology
  • Genetics

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