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


Polat E. G., Şeker M. E., Pervin B., Ulum B., Aerts Kaya F. S. F.

JOURNAL OF CELLULAR AND MOLECULAR MEDICINE, vol.29, no.15, pp.1-11, 2025 (SCI-Expanded, Scopus) identifier identifier

  • Publication Type: Article / Article
  • Volume: 29 Issue: 15
  • Publication Date: 2025
  • Doi Number: 10.1111/jcmm.70776
  • Journal Name: JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, BIOSIS, MEDLINE, Directory of Open Access Journals
  • Page Numbers: pp.1-11
  • Hacettepe University Affiliated: Yes

Abstract

Obesity increases the likelihood of metabolic diseases and can affect stem cell function negatively. Here, we aimed to elucidatethe mechanisms involved in the loss of stem cell function induced by obesity by assessing levels of oxidative stress (OS) andendoplasmic reticulum stress (ERS) in bone marrow-derived mesenchymal stromal cells (BM-MSCs) from healthy donors witha body mass index (BMI) of 25–30 (obese) and BMI > 30 (morbid obese). We assessed base levels of OS and ERS, activation ofcellular response mechanisms, and the effects of Melatonin (MT), which is known to decrease OS, and TUDCA, which is knownto decrease ERS. Loss of BM-MSC differentiation was correlated with the degree of obesity and associated with upregulation ofOS and ERS. Increased BMI was accompanied by elevated intracellular ROS and accelerated senescence of BM-MSCs. Althoughtreatment with MT and TUDCA was able to decrease OS and ERS in BM-MSCs from obese donors, cellular stress in BM-MSCsfrom morbid obese donors was irreversible. Therefore, it is imperative to treat and prevent obesity before the negative effects onstem cells become permanent and irreversible. Early treatment of obesity may not only prevent metabolic diseases; it may alsoprotect tissue resident stem cells