title: PDGFRα and CD51 mark human nestin+ sphere-forming mesenchymal stem cells capable of hematopoietic progenitor cell expansion.
abstract: The intermediate filament protein Nestin labels populations of stem/progenitor cells, including self-renewing mesenchymal stem cells (MSCs), a major constituent of the hematopoietic stem cell (HSC) niche. However, the intracellular location of Nestin prevents its use for prospective live cell isolation. Hence it is important to find surface markers specific for Nestin⁺ cells. In this study, we show that the expression of PDGFRα and CD51 among CD45⁻ Ter119⁻ CD31⁻ mouse bone marrow (BM) stromal cells characterizes a large fraction of Nestin⁺ cells, containing most fibroblastic CFUs, mesenspheres, and self-renewal capacity after transplantation. The PDGFRα⁺ CD51 ⁺subset of Nestin⁺ cells is also enriched in major HSC maintenance genes, supporting the notion that niche activity co-segregates with MSC activity. Furthermore, we show that PDGFRα⁺ CD51⁺ cells in the human fetal BM represent a small subset of CD146⁺ cells expressing Nestin and enriched for MSC and HSC niche activities. Importantly, cultured human PDGFRα⁺ CD51⁺ nonadherent mesenspheres can significantly expand multipotent hematopoietic progenitors able to engraft immunodeficient mice. These results thus indicate that the HSC niche is conserved between the murine and human species and suggest that highly purified nonadherent cultures of niche cells may represent a useful novel technology to culture human hematopoietic stem and progenitor cells.
authors.affiliation: Gottesman Institute for Stem Cell and Regenerative Medicine Research, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
authors.forename: Sandra
authors.initials: S
authors.lastname: Pinho
authors.forename: Julie
authors.initials: J
authors.lastname: Lacombe
authors.forename: Maher
authors.initials: M
authors.lastname: Hanoun
authors.forename: Toshihide
authors.initials: T
authors.lastname: Mizoguchi
authors.forename: Ingmar
authors.initials: I
authors.lastname: Bruns
authors.forename: Yuya
authors.initials: Y
authors.lastname: Kunisaki
authors.forename: Paul S
authors.initials: PS
authors.lastname: Frenette
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000502:physiology*; D006412:Hematopoietic Stem Cells / Q000145:classification / Q000166:cytology* / Q000378:metabolism*; D006801:Humans; D039564:Integrin alphaV / Q000378:metabolism*; D007381:Intermediate Filament Proteins / Q000096:biosynthesis*; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000145:classification / Q000166:cytology* / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D008822:Mice, Transgenic; D009419:Nerve Tissue Proteins / Q000096:biosynthesis*; D064231:Nestin; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000378:metabolism*; D018874:Spheroids, Cellular / Q000166:cytology / Q000378:metabolism; D019089:Stem Cell Factor / Q000378:metabolism; D055153:Stem Cell Niche / Q000235:genetics / Q000502:physiology
chemical_list: D039564:Integrin alphaV; D007381:Intermediate Filament Proteins; C577484:NES protein, human; D009419:Nerve Tissue Proteins; C577485:Nes protein, mouse; D064231:Nestin; D019089:Stem Cell Factor; D020796:Receptor, Platelet-Derived Growth Factor alpha