酸化对脂肪衍生的干细胞损伤和基因表达的影响
Kun Huang1, Qinqin Wang1, Huilong Qu1
1Department of Cardiology, Second Affiliated Hospital of Naval Medical University, Shanghai Cardiovascular Institute of Integrative Medicine, 200003 Shanghai, China.
酸性通过影响生存,增殖和功能,在关键肢体缺血中损害脂肪衍生干细胞 (ADSC). 向组织pH平衡和与酸化相关的基因可以改善缺血性疾病的干细胞治疗.
科学领域:
- 再生医学是一种再生医学.
- 细胞生物学 细胞生物学
- 缺血症研究 缺血症研究
背景情况:
- 使用干细胞治疗关键四肢缺血症 (CLI) 的临床试验取得了令人失望的结果.
- 缺血组织中的酸性微环境被假设限制了干细胞的生存和功能.
研究的目的:
- 用微透析来调查CLI中酸性和代谢失衡的存在.
- 探索细胞外化对脂肪衍生干细胞 (ADSC) 的分子和转录效应.
主要方法:
- 微透析用于评估严重缺血症中的酸性和代谢失衡.
- 脂肪基衍生干细胞 (ADSC) 被暴露在细胞外化中,以评估分子和转录反应.
- 进行了转录基因组分析,以确定受酸性疾病影响的关键信号通路和基因.
主要成果:
- 低pH显著抑制ADSC的增殖和生存,导致细胞循环停止.
- 酸化会导致线粒体功能障碍,DNA损伤,并以pH依赖的方式损害ADSCs的益血管性功能.
- 转录组分析揭示了关键的信号通路和枢纽基因,这些基因参与了细胞对酸性疾病的反应.
结论:
- 酸化在缺血性微环境中的ADSCs受损方面发挥着关键作用.
- 专注于恢复组织pH平衡的治疗策略和向酸性化介导的枢纽基因显示出增强基于干细胞的CLI疗法的潜力.
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