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., ...Daha Fazla

JOURNAL OF CELLULAR PHYSIOLOGY, cilt.233, sa.11, ss.8429-8436, 2018 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 233 Sayı: 11
  • Basım Tarihi: 2018
  • Doi Numarası: 10.1002/jcp.26804
  • Dergi Adı: JOURNAL OF CELLULAR PHYSIOLOGY
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Sayfa Sayıları: ss.8429-8436
  • Anahtar Kelimeler: 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
  • Hacettepe Üniversitesi Adresli: Evet

Özet

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.