[PDF][PDF] CD133+ renal stem cells always co-express CD24 in adult human kidney tissue

P Romagnani, G Remuzzi - Stem Cell Res, 2014 - core.ac.uk
Stem Cell Res, 2014core.ac.uk
We (Angelotti et al., 2012; Romagnani et al., 2013; Ronconi et al., 2009; Sagrinati et al.,
2006) and others (Lindgren et al., 2011; Sallustio et al., 2013) previously demonstrated that
in fresh renal tissue, adult human kidneys contain a population of renal stem and more
committed progenitor cells characterized by co-expression of surface markers CD133 and
CD24. These cells can be expanded in culture while maintaining their phenotype, and they
exhibit self-renewal potential as well as the capacity to differentiate into podocytes and …
We (Angelotti et al., 2012; Romagnani et al., 2013; Ronconi et al., 2009; Sagrinati et al., 2006) and others (Lindgren et al., 2011; Sallustio et al., 2013) previously demonstrated that in fresh renal tissue, adult human kidneys contain a population of renal stem and more committed progenitor cells characterized by co-expression of surface markers CD133 and CD24. These cells can be expanded in culture while maintaining their phenotype, and they exhibit self-renewal potential as well as the capacity to differentiate into podocytes and tubular cells both in vitro and in vivo (Angelotti et al., 2012; Lindgren et al., 2011; Romagnani et al., 2013; Ronconi et al., 2009; Sagrinati et al., 2006; Sallustio et al., 2013). Consistently, CD133+ renal cells represent a subset of CD24+ cells during human kidney development, when they constitute the metanephric mesenchyme-derived primordial nephron (Lazzeri et al., 2007). In their manuscript published in the August issue of Stem Cell Research, Bombelli et al. describe the isolation of putative novel renal stem cells by culturing nephrosphere suspensions from adult human kidneys (Bombelli et al., 2013). Based on our previous studies, Bombelli et al. analyze nephrosphere-derived cells for expression of CD133 and CD24. The authors report the existence within nephrospheres of a CD133+ and CD24+ podocyte progenitor and also propose the existence of a CD133+ renal stem cell population that does not express CD24 (Bombelli et al., 2013). However, in their study the authors limit their analysis to the population that they derived after nephrosphere cultures and do not check for the actual existence of CD133+/CD24− cells in adult human kidney tissues. Indeed, as already reported (Angelotti et al., 2012; Ronconi et al., 2009; Sagrinati et al., 2006), after depletion of hematopoietic cells using the pan-haematopoietic marker CD45, all the CD133+ cells observed in adult human kidney tissue are CD24+(Fig. 1). Thus, CD133+/CD24− cells do not exist in vivo (Angelotti et al., 2012; Ronconi et al., 2009; Sagrinati et al., 2006). The authors' results may have two possible explanations: 1) The staining for CD24 performed by direct fluorescent labeling and using a different anti-CD24 antibody in FACS analysis may have reduced sensitivity and what the authors see as CD133+ CD24− are cells that express low levels of CD24, and 2) Prolonged culture in suspension before analysis (at least 10 days, as reported by the authors) may have modified the cell phenotype. However, the latter hypothesis is unlikely, since culture of nephrospheres was previously reported to enrich a cell with a CD133+/CD24+ phenotype by Buzhor et al.(Buzhor et al., 2011). In summary, we would like to underline that although diverse methods may be used to identify putative renal stem or progenitor cells in adult human kidneys and study their properties, it is ultimately important to establish the existence of the putative stem cell population in fresh kidney tissue,
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