Low/Negative Expression of PDGFR-α Identifies the Candidate Primary Mesenchymal Stromal Cells in Adult Human Bone Marrow

Summary

Human bone marrow (BM) contains a rare population of nonhematopoietic mesenchymal stromal cells (MSCs), which are of central importance for the hematopoietic microenvironment. However, the precise phenotypic definition of these cells in adult BM has not yet been reported. In this study, we show that low/negative expression of CD140a (PDGFR-α) on lin ⁻/CD45 ⁻/CD271 ⁺ BM cells identified a cell population with very high MSC activity, measured as fibroblastic colony-forming unit frequency and typical in vitro and in vivo stroma formation and differentiation capacities. Furthermore, these cells exhibited high levels of genes associated with mesenchymal lineages and HSC supportive function. Moreover, lin ⁻/CD45 ⁻/CD271 ⁺/CD140a ^low/− cells effectively mediated the ex vivo expansion of transplantable CD34 ⁺ hematopoietic stem cells. Taken together, these data indicate that CD140a is a key negative selection marker for adult human BM-MSCs, which enables to prospectively isolate a close to pure population of candidate human adult stroma stem/progenitor cells with potent hematopoiesis-supporting capacity.

Graphical Abstract

Highlights

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  Comparative gene expression profiling identified MSC markers

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  Primary adult bone marrow MSCs are CD140 (PDGFR-α) low/negative

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  CD140a ^low/− cells have typical in vitro and in vivo MSC properties

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  Coculture with CD140a ^low/− cells effectively expanded transplantable CD34 ⁺ HSCs

Abstract

Scheding and colleagues report that low/negative expression of PDGFR-α on lin ⁻/CD45 ⁻/CD271 ⁺ bone marrow cells identified a cell population with very high CFU-F activity, typical in vitro and in vivo MSC properties, and HSC supportive function. These data indicate that PDGFR-α is a key marker for adult human BM-MSCs, which are critical for the definition of the putative stroma stem cells.