Assessment of the Effects Of Melatonın on the Functıonal Defıcıts Induced by Cellular Stress in Obese Donor Derıved Mesenchymal Stem Cells
Özet
Obesity negatively affects different types of stem cells and BM-MSCs from individuals with a high BMI display a severely impaired differentiation capacity, reduced proliferation and increased ER stress. However, the role of oxidative stress (OS) in the development of obesity-related loss-of-stemness and the potential protective role of melatonin (MT) is currently unknown. Here, we evaluated ER stress, OS and senescence in BM-MSCs obtained from healthy (BMI 20-25), obese (BMI of 25-30) and morbid obese (BMI>30) donors. We assessed the proliferative and three- lineage differentiation potential of BM-MSCs in relation with BMI and we investigated whether treatment with MT with or without TUDCA can modulate ER stress, OS and improve cellular functions of obese donor-derived BM-MSCs. BM- MSCs obtained from all donors were morphologically and phenotypically similar. Obese and morbid obese donor-derived BM-MSCs display signs of increased ER stress and moderate OS, resulting in accelerated senescence, decreased proliferation, increased levels of ROS and decreased differentiation capacity. TUDCA partially reversed the effects of obesity-related loss-of-stem cell function. MT stimulated proliferation of healthy BM-MSCs, but was not able to recover loss-of-stemness. Neither TUDCA nor MT alone or in combination were sufficient to completely rescue the differentiation potential of obese donor-derived BM-MSCs. In conclusion, obesity-related loss-of-stem cell function can be contributed to increased ER stress and moderate OS, that can be partially treated with TUDCA.
