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

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.