Adaptive changes of adipose tissue to hypoxia : cell death-mediated activation of stem cells

脂肪组织对缺氧的适应性变化：细胞死亡介导的干细胞激活

• 批准号: 22659320
• 负责人: YOSHIMURA Kotaro
• 金额: $ 2.04万
• 依托单位: The University of Tokyo
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Challenging Exploratory Research
• 财政年份: 2010
• 资助国家: 日本
• 起止时间: 2010 至 2011
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-22659320/
• 关键词: 脂肪由来幹細胞; 血管内皮細胞; 虚血; 創傷治癒; 血管新生; 細胞死因子; 脂肪由来幹細胞; 血管内皮細胞; 虚血; 創傷治癒; 血管新生; 細胞死因子

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 therapeutic potentials of AIC. AIC preferentially activated adipose-derived stem/progenitor cells(ASCs) to proliferate, migrate, and form capillary networks compared to vascular endothelial cells, while VEGF did not induce mitogenesis or chemotaxis in hASCs. 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 other cell types. In ischemic adipose tissues of mice, induced either by a surgical intervention or by diabetes, AIC administration enhanced proliferation, especially of CD31-/CD34+ASCs, and mitigated tissue hypoxia by increasing capillary density and reducing fibrogenesis. These results suggested 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 with regard to morbidity, cost, and physical risks, and may be used for an alternative therapy for improving tissue oxygen tension.

基于对受伤脂肪组织的渗出液的分析，我们制备了一个混合物，该混合物与渗出液的比例相同，该混合物的比例与渗出液相同，称为脂肪损伤鸡尾酒（AIC）。我们假设AIC诱导一系列再生和血管生成过程而没有实际伤害。这项研究的目的是阐明AIC的治疗潜力。与血管内皮细胞相比，AIC优先活化的脂肪衍生的干茎/祖细胞（ASC）可以增殖，迁移和形成毛细血管网络，而VEGF在HASC中没有诱导有丝分裂遗传或趋化性。 AIC的每个成分生长因子都对ASC激活负有不同的原因。 AIC处理的ASC倾向于分化为脂肪细胞或血管构成细胞而不是其他细胞类型。在小鼠的缺血性脂肪组织中，通过手术干预或通过糖尿病诱导，AIC给药增强了增殖，尤其是CD31-/CD34+ASC的增殖，以及通过增加毛细血管密度和减少纤维发生的减轻组织缺氧。这些结果表明，通过通过激活ASC和其他细胞诱导脂肪重塑和新血管化，AIC可能具有各种缺血/低氧条件的治疗潜力。 AIC治疗在发病率，成本和身体风险方面比基于细胞的疗法具有许多优势，并且可以用于改善组织氧张力的替代疗法。