Polat Ece Gizem, Şeker Mehmet Emin, Pervin Burcu, Ulum Barış, Aerts-Kaya Fatima
Department of Stem Cell Sciences, Hacettepe University Graduate School of Health Sciences, Ankara, Turkey.
Hacettepe University Center for Stem Cell Research and Development, Ankara, Turkey.
J Cell Mol Med. 2025 Aug;29(15):e70776. doi: 10.1111/jcmm.70776.
Obesity increases the likelihood of metabolic diseases and can affect stem cell function negatively. Here, we aimed to elucidate the mechanisms involved in the loss of stem cell function induced by obesity by assessing levels of oxidative stress (OS) and endoplasmic reticulum stress (ERS) in bone marrow-derived mesenchymal stromal cells (BM-MSCs) from healthy donors with a body mass index (BMI) of 25-30 (obese) and BMI > 30 (morbid obese). We assessed base levels of OS and ERS, activation of cellular response mechanisms, and the effects of Melatonin (MT), which is known to decrease OS, and TUDCA, which is known to decrease ERS. Loss of BM-MSC differentiation was correlated with the degree of obesity and associated with upregulation of OS and ERS. Increased BMI was accompanied by elevated intracellular ROS and accelerated senescence of BM-MSCs. Although treatment with MT and TUDCA was able to decrease OS and ERS in BM-MSCs from obese donors, cellular stress in BM-MSCs from morbid obese donors was irreversible. Therefore, it is imperative to treat and prevent obesity before the negative effects on stem cells become permanent and irreversible. Early treatment of obesity may not only prevent metabolic diseases; it may also protect tissue resident stem cells.
肥胖会增加代谢性疾病的发生几率，并可能对干细胞功能产生负面影响。在此，我们旨在通过评估体重指数（BMI）为25 - 30（肥胖）和BMI > 30（病态肥胖）的健康供体的骨髓间充质基质细胞（BM - MSCs）中的氧化应激（OS）水平和内质网应激（ERS）水平，来阐明肥胖诱导干细胞功能丧失所涉及的机制。我们评估了OS和ERS的基础水平、细胞反应机制的激活情况，以及褪黑素（MT，已知可降低OS）和牛磺熊去氧胆酸（TUDCA，已知可降低ERS）的作用。BM - MSC分化的丧失与肥胖程度相关，并与OS和ERS的上调有关。BMI的增加伴随着BM - MSCs细胞内活性氧（ROS）的升高和衰老加速。尽管用MT和TUDCA处理能够降低肥胖供体BM - MSCs中的OS和ERS，但病态肥胖供体的BM - MSCs中的细胞应激是不可逆的。因此，在对干细胞的负面影响变得永久且不可逆之前，治疗和预防肥胖势在必行。早期治疗肥胖不仅可以预防代谢性疾病；还可能保护组织驻留干细胞。
