title: Characterization of human adipose tissue-resident hematopoietic cell populations reveals a novel macrophage subpopulation with CD34 expression and mesenchymal multipotency.
abstract: Adipose tissue (AT) is composed of mature adipocytes and stromal vascular fraction (SVF) cells, including adipose stem/stromal cells (ASCs). We characterized hematopoietic cells residing in human nonobese AT by analyzing the SVF isolated from human lipoaspirates and peripheral blood (PB). Flow cytometry revealed that AT-resident hematopoietic cells consisted of AT-resident macrophages (ATMs) or lymphocytes with a negligible number of granulocytes. AT-resident lymphocytes were composed of helper T cells and natural killer cells. Almost no B cells and few cytotoxic T cells were observed in nonobese AT. More than 90% of ATMs were M2 state CD206(+) macrophages (CD45(+)/CD14(+)) that were located in the periendothelium or interstitial spaces between adipocytes. We also discovered a novel subpopulation of CD34(+)/CD206(+) ATMs (11.1% of CD206(+)ATMs) that localized in the perivascular region. Microarray of noncultured CD34(+)/CD206(+) ATMs, CD34(-)/CD206(+) ATMs, CD45(-)/CD31(-)/CD34(+) ASCs, and PB-derived circulating monocytes revealed that CD34(+)/CD206(+) ATMs shared characteristics with ASCs and circulating monocytes. Unlike CD34(-)/CD206(+) ATMs, CD34(+)/CD206(+) ATMs could grow in adherent culture and were capable of differentiating into multiple mesenchymal (adipogenic, osteogenic, and chondrogenic) lineages, similar to ASCs. CD34(+)/CD206(+) ATMs grew rapidly and lost expression of CD45, CD14, and CD206 by passage 3, which resulted in a similar expression profile to ASCs. Thus, this novel ATM subpopulation (CD45(+)/CD14(+)/CD34(+)/CD206(+)) showed distinct biological properties from other ATMs and circulating monocytes/macrophages. The CD34(+)/CD206(+) ATMs possessed characteristics similar to ASCs, including adherence, localization, morphology, and mesenchymal multipotency. This AT-resident subpopulation may have migrated from the bone marrow and may be important to tissue maintenance and remolding.
authors.affiliation: Department of Plastic Surgery, University of Tokyo School of Medicine, Tokyo, Japan.
authors.forename: Hitomi
authors.initials: H
authors.lastname: Eto
authors.forename: Hisako
authors.initials: H
authors.lastname: Ishimine
authors.forename: Kahori
authors.initials: K
authors.lastname: Kinoshita
authors.forename: Kanako
authors.initials: K
authors.lastname: Watanabe-Susaki
authors.forename: Harunosuke
authors.initials: H
authors.lastname: Kato
authors.forename: Kentaro
authors.initials: K
authors.lastname: Doi
authors.forename: Shinichiro
authors.initials: S
authors.lastname: Kuno
authors.forename: Akira
authors.initials: A
authors.lastname: Kurisaki
authors.forename: Kotaro
authors.initials: K
authors.lastname: Yoshimura
mesh_terms: D050153:Abdominal Fat / Q000166:cytology*; D000328:Adult; D053687:Adult Stem Cells / Q000378:metabolism; D018952:Antigens, CD34 / Q000378:metabolism*; D002454:Cell Differentiation; D002478:Cells, Cultured; D006412:Hematopoietic Stem Cells / Q000378:metabolism*; D006801:Humans; D037181:Lectins, C-Type / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism*; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins / Q000378:metabolism; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D008875:Middle Aged; D011956:Receptors, Cell Surface / Q000378:metabolism; D059467:Transcriptome
chemical_list: D018952:Antigens, CD34; D037181:Lectins, C-Type; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins; D011956:Receptors, Cell Surface