Obesity-Induced Loss of Function of Bone Marrow Mesenchymal Stromal Cells Is Linked to Cellular Stress and Irreversible at Advanced Stages.

Abstract

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.