Perivascular support of human hematopoietic stem/progenitor cells

Mirko Corselli, Chee Jia Chin, Chintan Parekh, Arineh Sahaghian, Wenyuan Wang, Shundi Ge, Denis Evseenko, Xiaoyan Wang, Elisa Montelatici, Lorenza Lazzari, Gay M. Crooks, Bruno Péault

Research output: Contribution to journalArticlepeer-review

Abstract

Hematopoietic stem and progenitor cells (HSPCs) emerge and develop adjacent to blood vessel walls in the yolk sac, aorta-gonad-mesonephros region, embryonic liver, and fetal bone marrow. In adult mouse bone marrow, perivascular cells shape a "niche" for HSPCs. Mesenchymal stem/stromal cells (MSCs), which support hematopoiesis in culture, are themselves derived in part from perivascular cells. In order to define their direct role in hematopoiesis, we tested the ability of purified human CD146+ perivascular cells, as compared with unfractionated MSCs and CD146- cells, to sustain human HSPCs in coculture. CD146+ perivascular cells support the long-term persistence, through cell-to-cell contact and at least partly via Notch activation, of human myelolymphoid HSPCs able to engraft primary and secondary immunodeficient mice. Conversely, unfractionated MSCs and CD146- cells induce differentiation and compromise ex vivo maintenance of HSPCs. Moreover, CD146+ perivascular cells express, natively and in culture, molecular markers of the vascular hematopoietic niche. Unexpectedly, this dramatic, previously undocumented ability to support hematopoietic stem cells is present in CD146+ perivascular cells extracted from the nonhematopoietic adipose tissue.

Original languageEnglish
Pages (from-to)2891-2901
Number of pages11
JournalBlood
Volume121
Issue number15
DOIs
Publication statusPublished - Apr 11 2013

ASJC Scopus subject areas

  • Hematology
  • Biochemistry
  • Cell Biology
  • Immunology

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