Characterization of human adipose tissue-resident hematopoietic cell populations reveals a novel macrophage subpopulation with CD34 expression and mesenchymal multipotency.

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作者：

H Eto，H Ishimine，K Kinoshita，K Watanabe-Susaki，H Kato，K Doi，S Kuno，A Kurisaki，K Yoshimura

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摘要：

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.

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关键词：

Humans Macrophages Hematopoietic Stem Cells Cells, Cultured Lectins, C-Type Mannose-Binding Lectins Receptors, Cell Surface Antigens, CD34 Cell Differentiation Adult