Plasticity of Human Adipose Lineage Cells Toward Endothelial Cells

Abstract

Background— Adipose tissue development and remodeling are closely associated with the growth of vascular network. We hypothesized that adipose tissue may contain progenitor cells with angiogenic potential and that therapy based on adipose tissue-derived progenitor cells administration may constitute a promising cell therapy in patients with ischemic disease. Methods and Results— In mice, cultured stromal-vascular fraction (SVF) cells from adipose tissue have a great proangiogenic potential, comparable to that of bone marrow mononuclear cells in the mouse ischemic hindlimb model. Similarly, cultured human SVF cells differentiate into endothelial cells, incorporate into vessels, and promote both postischemic neovascularization in nude mice and vessel-like structure formation in Matrigel plug. In vitro, these cells represent a homogeneous population of CD34- and CD13-positive cells, which can spontaneously express the endothelial cell markers CD31 and von Willebrand factor when cultured in semisolid medium. Interestingly, dedifferentiated mature human adipocytes have the potential to rapidly acquire the endothelial phenotype in vitro and to promote neovascularization in ischemic tissue and vessel-like structure formation in Matrigel plug, suggesting that cells of endothelial and adipocyte phenotypes may have a common precursor. Conclusions— This study demonstrates, for the first time, that adipocytes and endothelial cells have a common progenitor. Such adipose lineage cells participate in vascular-like structure formation in Matrigel plug and enhance the neovascularization reaction in ischemic tissue. These results also highlight the concept that adipose lineage cells represent a suitable new cell source for therapeutic angiogenesis in ischemic disease.

Mesenchymal stem cells share molecular signature with mesenchymal tumor cells and favor early tumor growth in syngeneic mice

“…Compared with normal fibroblasts (McAlhany et al, 2003), MTCs have a dramatically enhanced capacity to promote angiogenesis (Orimo et al, 2005), and play a determining role in supporting tumor growth with blood supply (Bhowmick et al, 2004). Likewise, MSCs have exceptional proangiogenic potential, and are thought to have promise for the treatment of ischemic disease (Miranville et al, 2004;Planat-Benard et al, 2004;Cao et al, 2005).…”

Osteogenic differentiation of human adipose-derived stem cells: comparison of two different inductive media

“…Human adipose-derived stem cells (hASCs) have been shown to possess multilineage potential to differentiate into bone, cartilage, fat, muscle, endothelial and neural cells (Zuk et al, 2001;De Ugarte et al, 2003;Dudas et al, 2006;Dragoo et al, 2003;Planat-Benard et al, 2004;Choi et al, 2006). We here analyse the differentiation capacity of hASCs cultured in two different osteogenic-inductive media.…”

Thérapies cellulaires pro-angiogéniques dans le traitement des pathologies ischémiques

“…Le tissu adipeux est une source de différentes sous-populations de cellules souches/progénitrices utiles à la régénération cardiaque et à l'augmentation de la néovascularisation. Des cellules souches mésen-chymateuses et des CPE ont été isolées après digestion enzymatique du tissu adipeux et leurs effets bénéfiques ont été démontrés dans des modèles expérimentaux [8]. Plus récemment, plusieurs laboratoires ont isolé des cellules progénitrices dans le tissu cardiaque chez différencier en plusieurs types de cellules matures appartenant à des organes de natures distinctes, la plasticité cellulaire de la plupart des cellules souches adultes est moindre et celles-ci expriment probablement un phénotype déjà plus différencié.…”