CD105 Protein Depletion Enhances Human Adipose-derived Stromal Cell Osteogenesis through Reduction of Transforming Growth Factor β1 (TGF-β1) Signaling
CD105 Protein Depletion Enhances Human Adipose-derived Stromal Cell Osteogenesis through Reduction of Transforming Growth Factor β1 (TGF-β1) Signaling
复制标题
DOI：
10.1074/jbc.m111.256529
复制
发表时间：
2011-11-11
影响因子：
4.8
通讯作者：
Longaker, Michael T.
中科院分区：
文献类型：
--
作者：
Levi, Benjamin;Wan, Derrick C.;Longaker, Michael T.
临床上可用于修复和重建的骨来源受到自体移植物的可及性、尸体材料的感染风险以及合成替代品的耐用性的限制。基于细胞的骨骼再生方法有可能满足这一需求，而脂肪组织代表了开发此类疗法的有希望的来源。在这里，我们利用基于微流体的单细胞转录分析和荧光激活细胞分选（FACS）富集了源自人类皮下脂肪组织的成骨细胞亚群。单细胞转录谱的统计分析表明，内皮糖蛋白（CD105）的低表达与成骨基因表达增加的脂肪来源细胞亚群相关。与 CD105（高）或未分选的细胞相比，FACS 分选的 CD105（低）细胞表现出显着增强的体外成骨分化和体内骨再生。对内皮糖蛋白通路的评估表明，CD105（低）脂肪来源细胞中成骨作用的增强可能是由于鉴定出具有较低 TGF-β 1/Smad2 信号传导的亚群。因此，这些发现凸显了促进脂肪源性间充质细胞成骨以促进骨骼再生的潜在途径。
Clinically available sources of bone for repair and reconstruction are limited by the accessibility of autologous grafts, infectious risks of cadaveric materials, and durability of synthetic substitutes. Cell-based approaches for skeletal regeneration can potentially fill this need, and adipose tissue represents a promising source for development of such therapies. Here, we enriched for an osteogenic subpopulation of cells derived from human subcutaneous adipose tissue utilizing microfluidic-based single cell transcriptional analysis and fluorescence-activated cell sorting (FACS). Statistical analysis of single cell transcriptional profiles demonstrated that low expression of endoglin (CD105) correlated with a subgroup of adipose-derived cells with increased osteogenic gene expression. FACS-sorted CD105(low) cells demonstrated significantly enhanced in vitro osteogenic differentiation and in vivo bone regeneration when compared with either CD105(high) or unsorted cells. Evaluation of the endoglin pathway suggested that enhanced osteogenesis among CD105(low) adipose-derived cells is likely due to identification of a subpopulation with lower TGF-beta 1/Smad2 signaling. These findings thus highlight a potential avenue to promote osteogenesis in adipose-derived mesenchymal cells for skeletal regeneration.