Investigation of differentiation induction method of capillary endothelial cells and pericytes by using adipose derived stem cells

利用脂肪干细胞诱导毛细血管内皮细胞和周细胞分化的方法研究

• 批准号: 21791739
• 负责人: HIGASHINO Takuya
• 金额: $ 2.75万
• 依托单位: The University of Tokyo
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Young Scientists (B)
• 财政年份: 2009
• 资助国家: 日本
• 起止时间: 2009 至 2010
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-21791739/
• 关键词: AIC; 増殖因子; ASC; 血管新生治療; 血管内皮細胞増殖; 虚血脂肪組織; 糖尿病脂肪組織; 脂肪由来幹細胞; 血管新生

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). 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 endothelialcells. 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.

基于对受伤脂肪组织渗出液的分析，我们制备了一种含有与渗出液相同比例的损伤相关生长因子的混合物，命名为脂肪损伤鸡尾酒（AIC）。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 优先激活脂肪干细胞/祖细胞/基质细胞 (ASC) 进行增殖、迁移和形成网络。 AIC处理的ASC倾向于分化成脂肪细胞或血管构成细胞，而不是分化成其他细胞类型。在由手术干预或糖尿病引起的小鼠缺血性脂肪组织中，AIC 给药增强了增殖，尤其是 CD31-/CD34+ ASC 的增殖，并通过增加毛细血管密度和减少纤维形成来减轻组织缺氧。这些结果表明，AIC 可能通过激活 ASC 和其他细胞来诱导脂肪重塑和新血管形成，从而具有治疗各种缺血/缺氧病症的潜力。在发病率、成本和身体风险方面，AIC 治疗比基于细胞的疗法具有许多优势，并且可以用作改善组织氧的替代疗法。

项目成果

創傷治癒因子による脂肪由来幹細胞の活性化を利用した血管新生治療の開発

利用伤口愈合因子激活脂肪干细胞开发血管生成治疗

• 发表时间: 2009
• 作者: 谷岳人;臼井規朗;神山雅史;福澤正洋;江藤ひとみ;谷岳人;江藤ひとみ
• 通讯作者: 江藤ひとみ

急性虚血誘導時の組織内適応変化の解析

急性缺血诱导过程中组织适应性变化分析

• 发表时间: 2010

Adipose Injury-Associated Factors Mitigate Hypoxia in Ischemic Tissues through Activation of Adipose-Derived Stem/Progenitor/Stromal Cells and Induction of Angiogenesis

• DOI: 10.1016/j.ajpath.2011.01.032
• 发表时间: 2011-05-01
• 期刊: AMERICAN JOURNAL OF PATHOLOGY
• 影响因子: 6
• 作者: Eto, Hitomi;Suga, Hirotaka;Yoshimura, Kotaro
• 通讯作者: Yoshimura, Kotaro

Injury-associated growth factors improve ischemia through the activation of adipose-derived stem/progenitor cells in obese and non-obese mice

损伤相关生长因子通过激活肥胖和非肥胖小鼠的脂肪干细胞/祖细胞来改善缺血

• 发表时间: 2009
• 作者: 谷岳人;臼井規朗;神山雅史;福澤正洋;江藤ひとみ
• 通讯作者: 江藤ひとみ