TY - JOUR
T1 - Direct reprogramming of human bone marrow stromal cells into functional renal cells using cell-free extracts
AU - Papadimou, Evangelia
AU - Morigi, Marina
AU - Iatropoulos, Paraskevas
AU - Xinaris, Christodoulos
AU - Tomasoni, Susanna
AU - Benedetti, Valentina
AU - Longaretti, Lorena
AU - Rota, Cinzia
AU - Todeschini, Marta
AU - Rizzo, Paola
AU - Introna, Martino
AU - De Simoni, Maria Grazia
AU - Remuzzi, Giuseppe
AU - Goligorsky, Michael S.
AU - Benigni, Ariela
PY - 2015
Y1 - 2015
N2 - 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.
AB - 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.
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U2 - 10.1016/j.stemcr.2015.02.002
DO - 10.1016/j.stemcr.2015.02.002
M3 - Article
AN - SCOPUS:84933671669
VL - 4
SP - 685
EP - 698
JO - Stem Cell Reports
JF - Stem Cell Reports
SN - 2213-6711
IS - 4
ER -