Bone marrow mesenchymal stem cell donors with a high body mass index display elevated endoplasmic reticulum stress and are functionally impaired

ULUM B. B. , TEKER H. T. , SARIKAYA A., BALTA G. , Kuskonmaz B., UCKAN-CETINKAYA D. , ...More

JOURNAL OF CELLULAR PHYSIOLOGY, vol.233, no.11, pp.8429-8436, 2018 (Journal Indexed in SCI) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 233 Issue: 11
  • Publication Date: 2018
  • Doi Number: 10.1002/jcp.26804
  • Page Numbers: pp.8429-8436
  • Keywords: 4-phenylbutyrate, body mass index, bone marrow mesenchymal stem cells, endoplasmic reticulum stress, tauroursodeoxycholic acid, UNFOLDED PROTEIN RESPONSE, DIET-INDUCED OBESITY, ADIPOSE-TISSUE, TAUROURSODEOXYCHOLIC ACID, ER STRESS, OSTEOGENIC DIFFERENTIATION, HEMATOPOIESIS, ADIPOGENESIS


Bone marrow mesenchymal stem cells (BM-MSCs) are promising candidates for regenerative medicine purposes. The effect of obesity on the function of BM-MSCs is currently unknown. Here, we assessed how obesity affects the function of BM-MSCs and the role of endoplasmic reticulum (ER) stress and the unfolded protein response (UPR) therein. BM-MSCs were obtained from healthy donors with a normal (<25) or high (>30) body mass index (BMI). High-BMI BM-MSCs displayed severely impaired osteogenic and diminished adipogenic differentiation, decreased proliferation rates, increased senescence, and elevated expression of ER stress-related genes ATF4 and CHOP. Suppression of ER stress using tauroursodeoxycholic acid (TUDCA) and 4-phenylbutyrate (4-PBA) resulted in partial recovery of osteogenic differentiation capacity, with a significant increase in the expression of ALPL and improvement in the UPR. These data indicate that BMI is important during the selection of BM-MSC donors for regenerative medicine purposes and that application of high-BMI BM-MSCs with TUDCA or 4-PBA may improve stem cell function. However, whether this improvement can be translated into an in vivo clinical advantage remains to be assessed.