DeWitt Daughtry Family Department of Surgery, University of Miami Leonard M. Miller School of Medicine, Miami, FL 33136, USA.
DeWitt Daughtry Family Department of Surgery, University of Miami Leonard M. Miller School of Medicine, Miami, FL 33136, USA.
Mol Ther. 2022 Feb 2;30(2):947-962. doi: 10.1016/j.ymthe.2021.06.020. Epub 2021 Jun 24.
Despite increasing interest in the reversal of age-related processes, there is a paucity of data regarding the effects of post-menopausal-associated estrogen loss on cellular function. We studied human adipose-derived mesenchymal stem cells (hASCs) isolated from women younger than 45 years old (pre-menopause, pre-hASC) or older than 55 years old (post-menopause, post-hASC). In this study, we provide proof of concept that the age-related ineffective functionality of ASCs can be reversed to improve their ability in promoting tissue repair. We found reduced estrogen receptor expression, decreased estrogen receptor activation, and reduced sensitivity to 17β-estradiol in post-hASCs. This correlated with decreased antioxidants (catalase and superoxide dismutase [SOD] expression) and increased oxidative stress compared with pre-hASCs. Increasing catalase expression in post-hASCs restored estrogen receptor (ER) expression and their functional capacity to promote tissue repair as shown in human skin ex vivo wound healing and in vivo mouse model of lung injury. Our results suggest that the consequences of 17β-estradiol decline on the function of hASCs may be reversible by changing the oxidative stress/antioxidant composition.
尽管人们对逆转与年龄相关的过程越来越感兴趣，但关于绝经后雌激素丧失对细胞功能的影响的数据却很少。我们研究了从年龄小于 45 岁的女性（绝经前，pre-hASC）或年龄大于 55 岁的女性（绝经后，post-hASC）中分离出的人脂肪间充质干细胞（hASC）。在这项研究中，我们提供了概念验证，证明 ASC 的与年龄相关的无效功能可以逆转，以提高其促进组织修复的能力。我们发现 post-hASC 中的雌激素受体表达减少，雌激素受体激活减少，对 17β-雌二醇的敏感性降低。这与 pre-hASC 相比，抗氧化剂（过氧化氢酶和超氧化物歧化酶[SOD]表达）减少和氧化应激增加有关。在 post-hASC 中增加过氧化氢酶的表达可恢复雌激素受体（ER）的表达及其促进组织修复的功能能力，如在人体皮肤 ex vivo 伤口愈合和体内小鼠肺损伤模型中所示。我们的研究结果表明，通过改变氧化应激/抗氧化剂组成，17β-雌二醇下降对 hASC 功能的影响可能是可逆的。
