PDGFRα and CD51 mark human Nestin+ sphere-forming mesenchymal stem cells capable of hematopoietic progenitor cell expansion

Sandra Pinho, Julie Lacombe, Maher Hanoun, Toshihide Mizoguchi, Ingmar Bruns, Yuya Kunisaki, Paul S. Frenette

Research output: Contribution to journalArticle

212 Citations (Scopus)

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 PDGFR? 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 PDGFR?+ 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 PDGFR?+ 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 PDGFR?+ 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.

Original languageEnglish
Pages (from-to)1351-1367
Number of pages17
JournalJournal of Experimental Medicine
Volume210
Issue number7
DOIs
Publication statusPublished - Jul 1 2013
Externally publishedYes

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Nestin
Hematopoietic Stem Cells
Mesenchymal Stromal Cells
Stem Cell Niche
Stem Cells
Intermediate Filament Proteins
Cell Separation
Cell Culture Techniques
Transplantation
Bone Marrow
Maintenance
Technology
Population
Genes

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

Cite this

PDGFRα and CD51 mark human Nestin+ sphere-forming mesenchymal stem cells capable of hematopoietic progenitor cell expansion. / Pinho, Sandra; Lacombe, Julie; Hanoun, Maher; Mizoguchi, Toshihide; Bruns, Ingmar; Kunisaki, Yuya; Frenette, Paul S.

In: Journal of Experimental Medicine, Vol. 210, No. 7, 01.07.2013, p. 1351-1367.

Research output: Contribution to journalArticle

Pinho, Sandra ; Lacombe, Julie ; Hanoun, Maher ; Mizoguchi, Toshihide ; Bruns, Ingmar ; Kunisaki, Yuya ; Frenette, Paul S. / PDGFRα and CD51 mark human Nestin+ sphere-forming mesenchymal stem cells capable of hematopoietic progenitor cell expansion. In: Journal of Experimental Medicine. 2013 ; Vol. 210, No. 7. pp. 1351-1367.
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