IFATS Collection: Identification of Hemangioblasts in the Adult Human Adipose Tissue

Abstract

The stromal-vascular fraction (SVF) of human adipose tissue contains, among other cell types, mesenchymal stem cells and precursors of adipocyte and endothelial cells. Here we show that, in addition, the nonhematopoietic fraction of the SVF has hematopoietic activity, since all types of hematopoietic colony-forming units (CFUs) developed when cultured in methylcellulose-based medium. This hematopoietic activity was restricted to the CD45 ؊ CD105 ؉ cell subset, well correlated with KDR ؉ cell content, and increased after culture with a combination of early-acting hematopoietic cytokines. Most of the CD45 ؊ KDR ؉ CD105 ؉ cells were nonadherent and did not express CD31, and this subset included both CD34؊ and CD34 ؉ cells. Moreover, these nonadherent cells migrated in response to KDR gradient, and when they were cultured in the presence of both hematopoietic and endothelial growth factors, a wave of CFUs was followed by a wave of mixed colonies comprising adherent elongated and nonadherent round hematopoietic cells. These mixed hematopoietic-endothelial (Hem-End) colonies were able to generate secondary Hem-End colonies and exhibited both hematopoietic and endothelial activity, as demonstrated by in vitro functional assays. These findings demonstrate for the first time the existence of primitive mesodermal progenitors within the SVF of human adipose tissue that exhibit in vitro hematopoietic and hemangioblastic activities, susceptible to being used in cell therapy and basic cell research.

De novo generation of white adipocytes from the myeloid lineage via mesenchymal intermediates is age, adipose depot, and gender specific

“…Terminal differentiation of these cells results in de novo generation of BMP-derived adipocytes. Alternatively, hematopoietic stem cells (HSCs) that reside in adipose tissue (23)(24)(25) might also serve as a resident source of white adipocytes. However, there are arguments against this alternative model.…”

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

“…In fact, 1 report demonstrated that murine adipose-derived hematopoietic stem/ progenitor cells contain precursors committed to the mast cell lineage [17]. Another report demonstrated the existence of hemangioblasts in human AT that exhibit the capacity for hematopoietic and endothelial differentiation in vitro [18].…”

Adipose tissue is an extramedullary reservoir for functional hematopoietic stem and progenitor cells

“…27 However, it was suggested that transplanted SVF contributed to the rebound of endogenous hematopoiesis rather than its own hematopoietic functions in the recipients. Moreover, a recent report 28 revealed that cultured SVF contains hemangioblasts, which have a bipotential capacity to differentiate into both endothelial cells and hematopoietic cells in vitro. However, the study focused on the potency of cultured SVF for hematopoiesis in vitro, instead of freshly isolated SVF.…”