The reprogramming efficiency was 0

The reprogramming efficiency was 0.01%C0.02%. as one of the most promising approaches of regenerative medicine (Riazi et?al., 2009). In the kidney field, the search for a renal-specific stem cell led to the discovery of progenitor cells that protect animals from acute kidney injury (AKI) when systemically infused (Angelotti et?al., 2012; Benigni et?al., 2010). However, the cell number is usually a limiting factor, and their biology is usually far from known. Therefore, other non-renal stem cell sources have been pursued. Derivation of human embryonic stem cells (hESCs) (Thomson et?al., 1998) has raised hope because they can give rise to all three germ layers, but progress toward somatic populations has encountered major obstacles, including the risk of cancer and rejection, not to mention the ethical issues involved. The same holds true for induced pluripotent stem cells (iPSCs) (Takahashi and Yamanaka, 2006), which are similar to hESCs but devoid of at least some of the above problems. The generation of hESC/iPSC-derived mature renal cells (Track et?al., 2012) and, more recently, intermediate mesoderm/metanephric mesenchyme (MM) and ureteric bud (UB) renal progenitors (Lam et?al., 2014; Lin et?al., 2010; Mae et?al., 2013; Takasato et?al., 2014) has been reported. In theory, patient-specific cells to be used therapeutically could be obtained through reprogramming approaches in which a long-standing interest exists because of the possibility that abundant adult cells can easily be harvested and converted to other cell types (Zhou CCK2R Ligand-Linker Conjugates 1 et?al., 2008). In this context, studies have defined sets of transcription factors that can directly reprogram somatic cells into another cell type without passing through the pluripotent state (Ginsberg et?al., 2012; Ieda et?al., 2010; Karow et?al., 2012; Vierbuchen et?al., 2010). Using a strategy of re-expressing key developmental regulators in?vitro/in?vivo, adult cell reprogramming occurs, through which induced cells residing in their native environment might promote their survival and/or maturation (Ginsberg et?al., 2012; Ieda et?al., 2010; Karow et?al., 2012; Qian et?al., 2012; Vierbuchen CCK2R Ligand-Linker Conjugates 1 et?al., 2010; Zhou et?al., 2008). In parallel with these developments, an intriguing technology for direct cell reprogramming by exposing reversibly permeabilized somatic cells to cell-free extracts has emerged. This method has its origins in the early experiments of Briggs and King, followed by Gurdon (Gurdon, 2006), where a somatic cell nucleus was transferred (SCNT [somatic cell nuclear transfer]) to an enucleated oocyte, resulting in the activation of the somatic cell nucleus. Cell-extract reprogramming was first exhibited with extracts of regenerating newt limbs, which promoted cell-cycle re-entry and downregulation of myogenic markers in differentiated myotubes (McGann et?al., 2001). Afterward, this approach yielded in-vitro-reprogrammed somatic cells with the extracts from T?cells, cardiomyocytes, insulinoma cells, pneumocytes, chromaffin, or embryonic stem cells (Gaustad et?al., 2004; H?kelien et?al., 2002, 2004; Landsverk et?al., 2002; Qin et?al., 2005; Qu et?al., 2013; Rajasingh et?al., 2008). Surprisingly, there is a paucity of attempts at the reverse reprogramming of adult stem cells toward somatic cells. Human bone marrow stromal cells (BMSCs), also known as bone-marrow-derived mesenchymal stem cells, are adult stem/progenitor cells with self-renewal capacity and restricted potential for generating skeletal tissues, including G-CSF osteoblast, chondrocyte, adipocyte, and perivascular stromal cells (Bianco et?al., 2013; Le Blanc and Mougiakakos, 2012). Whether BMSCs can be used therapeutically is still a matter of debate. Based on their paracrine action rather than differentiation ability, these cells have been used with CCK2R Ligand-Linker Conjugates 1 promising results in different diseases (Le Blanc and Mougiakakos, 2012; Morigi and Benigni, 2013; Reinders et?al., 2014; Souidi et?al., 2013). No evidence of direct reprogramming of BMSCs into somatic cells is usually available yet. Here, we inquired whether human BMSCs could be reverse reprogrammed to acquire a renal tubular epithelial phenotype by using tubular cell extracts. We found that reprogrammed BMSCs (1) acquired an antigenic profile and functional properties of proximal tubular-like epithelial cells in?vitro,.

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