Adipose Injury-Associated Factors Mitigate Hypoxia in Ischemic Tissues through Activation of Adipose-Derived Stem/Progenitor/Stromal Cells and Induction of Angiogenesis
Adipose Injury-Associated Factors Mitigate Hypoxia in Ischemic Tissues through Activation of Adipose-Derived Stem/Progenitor/Stromal Cells and Induction of Angiogenesis
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DOI：
10.1016/j.ajpath.2011.01.032
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发表时间：
2011-05-01
影响因子：
6
通讯作者：
Yoshimura, Kotaro
中科院分区：
文献类型：
--
作者：
Eto, Hitomi;Suga, Hirotaka;Yoshimura, Kotaro
在对损伤脂肪组织渗出液进行分析的基础上，我们制备了一种含有损伤相关生长因子的混合物，命名为脂肪损伤鸡尾酒(AIC)。我们假设AIC在没有实际损伤的情况下诱导了一系列的再生和血管生成过程。本研究的目的是阐明AIC的治疗潜力。与血管内皮细胞相比，AIC优先激活脂肪来源的干/祖/基质细胞(ASCs)增殖、迁移和形成网络，而血管内皮生长因子不诱导ASCs的有丝分裂或趋化作用。AIC各组分生长因子对ASC激活的作用不同。AIC处理的ASCs倾向于分化为脂肪细胞或血管形成细胞，而不是其他类型的细胞。在手术干预或糖尿病诱导的小鼠缺血脂肪组织中，AIC促进了ASCs的增殖，尤其是CD31(-)/CD34(+)ASCs，并通过增加毛细血管密度和减少纤维化来减轻组织缺氧。这些结果表明，AIC可能通过激活ASCs和其他细胞而诱导脂肪重塑和新生血管，从而对各种缺血/缺氧情况具有治疗潜力。与基于细胞的疗法相比，AIC疗法在发病率、成本和物理风险方面具有许多优势，可以作为一种改善组织氧气的替代疗法。(Am J Pathol2011,178：2322-2332；10.1016/j.ajpath.2011.01.032)
Based on the analysis of exudates from injured adipose tissue, we prepared a mixture containing the injury-associated growth factors at the same proportion as the exudates, named adipose injury cocktail (AIC). We hypothesized that AIC induces a series of regenerating and angiogenic processes without actual wounding. The purpose of this study is to elucidate the therapeutic potentials of AIC. AIC preferentially activated adipose-derived stem/progenitor/stromal cells (ASCs) to proliferate, migrate, and form networks compared with vascular endothelial cells, whereas vascular endothelial growth factor did not induce mitogenesis or chemotaxis in human ASCs. Each component growth factor of AIC was differently responsible for the ASC activation. AIC-treated ASCs tended to differentiate into adipocytes or vessel-constituting cells rather than into other cell types. In ischemic adipose tissues of mice, induced by either a surgical intervention or diabetes, AIC administration enhanced proliferation, especially of CD31(-)/CD34(+) ASCs, and mitigated tissue hypoxia by increasing capillary density and reducing fibrogenesis. These results suggest that AIC may have therapeutic potentials for various ischemic/hypoxic conditions by inducing adipose remodeling and neovascularization through activation of ASCs and other cells. Treatment with AIC has many advantages over cell-based therapies regarding morbidity, cost, and physical risks and may be used as an alternative therapy for improving tissue oxygen. (Am J Pathol 2011, 178:2322-2332; 10.1016/j.ajpath.2011.01.032)