Direct reprogramming of human bone marrow stromal cells into functional renal cells using cell-free extracts.
Bottom Line: 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.Thus, reprogrammed BMSCs are a promising cell resource for future cell therapy.
Affiliation: IRCCS-Istituto di Ricerche Farmacologiche "Mario Negri," Centro Anna Maria Astori, Science and Technology Park Kilometro Rosso, 24126 Bergamo, Italy. Electronic address: firstname.lastname@example.org.Show MeSH
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Mentions: To assess the functional integration into kidney tissue, human cells (CL17, HK2, or BMSCs) were mixed with kidney cells derived from embryonic day 11.5 (E11.5) mice (Unbekandt and Davies, 2010; Xinaris et al., 2012), and grown as explants for 5 days. At day 1, CL17 cells integrated into the condensing metanephric mesenchyme that was identified by co-expression of neural cell adhesion molecule (NCAM) and PAX2 markers (Figure 5A, insert). At day 5, chimeric aggregates of human and mouse cells grew into elongating tubular structures that were surrounded by laminin-positive basement membranes (Figures 5B and 5C). Remarkably, tubular structures containing CL17 or HK2 cells were in close vicinity to glomerular-like structures expressing the early podocyte marker Wilms tumor 1 (WT1) (Figures 5E and 5F). BMSCs neither formed nor contributed to renal structures, indicating non-nephrogenic potential (Figures 5D and 5G).
Affiliation: IRCCS-Istituto di Ricerche Farmacologiche "Mario Negri," Centro Anna Maria Astori, Science and Technology Park Kilometro Rosso, 24126 Bergamo, Italy. Electronic address: email@example.com.