Planat-Benard Valérie, Silvestre Jean-Sébastien, Cousin Béatrice, André Mireille, Nibbelink Maryse, Tamarat Radia, Clergue Michel, Manneville Carole, Saillan-Barreau Corinne, Duriez Micheline, Tedgui Alain, Levy Bernard, Pénicaud Luc, Casteilla Louis
Unité Mixte de Recherche 5018 Centre National de la Recherche Scientifique, Université Paul Sabatier, Centre Hospitalier Universitaire Rangueil, Toulouse, France.
Circulation. 2004 Feb 10;109(5):656-63. doi: 10.1161/01.CIR.0000114522.38265.61. Epub 2004 Jan 20.
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.
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.
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.
脂肪组织的发育和重塑与血管网络的生长密切相关。我们推测脂肪组织可能含有具有血管生成潜能的祖细胞，基于脂肪组织来源的祖细胞给药的治疗可能成为缺血性疾病患者一种有前景的细胞治疗方法。
在小鼠中，在小鼠缺血后肢模型中，培养的脂肪组织基质血管成分（SVF）细胞具有强大的促血管生成潜能，与骨髓单个核细胞相当。同样，培养的人SVF细胞可分化为内皮细胞，整合到血管中，并促进裸鼠缺血后新血管形成以及基质胶栓中血管样结构的形成。在体外，这些细胞代表CD34和CD13阳性的同质细胞群，当在半固体培养基中培养时，它们可自发表达内皮细胞标志物CD31和血管性血友病因子。有趣的是，去分化的成熟人脂肪细胞在体外有迅速获得内皮表型的潜能，并能促进缺血组织中的新血管形成以及基质胶栓中血管样结构的形成，这表明内皮细胞和脂肪细胞表型的细胞可能有共同的前体细胞。
本研究首次证明脂肪细胞和内皮细胞有共同的祖细胞。这类脂肪谱系细胞参与基质胶栓中血管样结构的形成，并增强缺血组织中的新血管形成反应。这些结果还突出了这样一个概念，即脂肪谱系细胞是缺血性疾病治疗性血管生成的合适新细胞来源。
