Characterization of Human Adipose Tissue-Resident Hematopoietic Cell Populations Reveals a Novel Macrophage Subpopulation with CD34 Expression and Mesenchymal Multipotency

<jats:p> 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 <jats:sup>+</jats:sup> macrophages (CD45 <jats:sup>+</jats:sup> /CD14 <jats:sup>+</jats:sup> ) that were located in the periendothelium or interstitial spaces between adipocytes. We also discovered a novel subpopulation of CD34 <jats:sup>+</jats:sup> /CD206 <jats:sup>+</jats:sup> ATMs (11.1% of CD206 <jats:sup>+</jats:sup> ATMs) that localized in the perivascular region. Microarray of noncultured CD34 <jats:sup>+</jats:sup> /CD206 <jats:sup>+</jats:sup> ATMs, CD34 <jats:sup>−</jats:sup> /CD206 <jats:sup>+</jats:sup> ATMs, CD45 <jats:sup>−</jats:sup> /CD31 <jats:sup>−</jats:sup> /CD34 <jats:sup>+</jats:sup> ASCs, and PB-derived circulating monocytes revealed that CD34 <jats:sup>+</jats:sup> /CD206 <jats:sup>+</jats:sup> ATMs shared characteristics with ASCs and circulating monocytes. Unlike CD34 <jats:sup>−</jats:sup> /CD206 <jats:sup>+</jats:sup> ATMs, CD34 <jats:sup>+</jats:sup> /CD206 <jats:sup>+</jats:sup> ATMs could grow in adherent culture and were capable of differentiating into multiple mesenchymal (adipogenic, osteogenic, and chondrogenic) lineages, similar to ASCs. CD34 <jats:sup>+</jats:sup> /CD206 <jats:sup>+</jats:sup> 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 <jats:sup>+</jats:sup> /CD14 <jats:sup>+</jats:sup> /CD34 <jats:sup>+</jats:sup> /CD206 <jats:sup>+</jats:sup> ) showed distinct biological properties from other ATMs and circulating monocytes/macrophages. The CD34 <jats:sup>+</jats:sup> /CD206 <jats:sup>+</jats:sup> 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. </jats:p>