title: Perivascular support of human hematopoietic stem/progenitor cells.
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.
authors: Orthopaedic Hospital, Department of Orthopaedic Surgery, University of California at Los Angeles (UCLA), CA, USA.
authors: Mirko
authors: M
authors: Corselli
authors: Chee Jia
authors: CJ
authors: Chin
authors: Chintan
authors: C
authors: Parekh
authors: Arineh
authors: A
authors: Sahaghian
authors: Wenyuan
authors: W
authors: Wang
authors: Shundi
authors: S
authors: Ge
authors: Denis
authors: D
authors: Evseenko
authors: Xiaoyan
authors: X
authors: Wang
authors: Elisa
authors: E
authors: Montelatici
authors: Lorenza
authors: L
authors: Lazzari
authors: Gay M
authors: GM
authors: Crooks
authors: Bruno
authors: B
authors: Péault
mesh_terms: D000328:Adult; D000818:Animals; D018952:Antigens, CD34 / Q000378:metabolism; D001808:Blood Vessels / Q000166:cytology / Q000502:physiology*; D015153:Blotting, Western; D051929:CD146 Antigen / Q000378:metabolism*; D002135:Calcium-Binding Proteins / Q000235:genetics / Q000378:metabolism; D002450:Cell Communication; D002478:Cells, Cultured; D054377:Chemokine CXCL12 / Q000235:genetics / Q000378:metabolism; D018920:Coculture Techniques; D005312:Fetal Blood / Q000166:cytology / Q000378:metabolism; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000378:metabolism* / Q000502:physiology*; D006801:Humans; D007150:Immunohistochemistry; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D007381:Intermediate Filament Proteins / Q000235:genetics / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism / Q000502:physiology; D051379:Mice; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D064231:Nestin; D051880:Receptors, Notch / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000072099:Serrate-Jagged Proteins
chemical_list: D018952:Antigens, CD34; D051929:CD146 Antigen; D002135:Calcium-Binding Proteins; D054377:Chemokine CXCL12; D036341:Intercellular Signaling Peptides and Proteins; D007381:Intermediate Filament Proteins; D008565:Membrane Proteins; C577484:NES protein, human; D009419:Nerve Tissue Proteins; C577485:Nes protein, mouse; D064231:Nestin; D051880:Receptors, Notch; D000072099:Serrate-Jagged Proteins