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Perivascular support of human hematopoietic stem/progenitor cells.

TitlePerivascular support of human hematopoietic stem/progenitor cells.
Publication TypeJournal Article
Year of Publication2013
AuthorsCorselli M, Chin CJia, Parekh C, Sahaghian A, Wang W, Ge S, Evseenko D, Wang X, Montelatici E, Lazzari L, Crooks GM, Péault B
JournalBlood
Volume121
Issue15
Pagination2891-901
Date Published2013 Apr 11
ISSN1528-0020
KeywordsAdult, Animals, Antigens, CD146, Antigens, CD34, Blood Vessels, Blotting, Western, Calcium-Binding Proteins, Cell Communication, Cells, Cultured, Chemokine CXCL12, Coculture Techniques, Fetal Blood, Hematopoietic Stem Cells, Humans, Immunohistochemistry, Intercellular Signaling Peptides and Proteins, Intermediate Filament Proteins, Membrane Proteins, Mesenchymal Stromal Cells, Mice, Nerve Tissue Proteins, Nestin, Receptors, Notch, Reverse Transcriptase Polymerase Chain Reaction
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.

DOI10.1182/blood-2012-08-451864
Alternate JournalBlood
PubMed ID23412095
PubMed Central IDPMC3707421
Grant ListG1000816 / / Medical Research Council / United Kingdom
K01 AR061415 / AR / NIAMS NIH HHS / United States
P30 CA016042 / CA / NCI NIH HHS / United States
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