Bone Marrow Mesenchymal Stem Cells from Donors with a High BMI Display ER Stress and Are Functionally Impaired.

Ulum B., Teker H. T., Sarıkaya A., BALTA G., KUŞKONMAZ B. B., ÇETİNKAYA F. D., ...More

JOURNAL OF CELLULAR PHYSIOLOGY, vol.2018, pp.1-8, 2018 (SCI-Expanded)

  • Publication Type: Article / Letter
  • Volume: 2018
  • Publication Date: 2018
  • Journal Name: JOURNAL OF CELLULAR PHYSIOLOGY
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Page Numbers: pp.1-8
  • Hacettepe University Affiliated: Yes

Abstract

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 un known. Here, we assessed how obesity affects the function of BM‐MSCs and

the role of endoplasmic reticulum ( ER) stress and the unfolded prote in 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 senes-

cence, and elevated expression of ER stress–related genes ATF4 and CHOP. Suppression

of ER stress using taurourso deoxycholic 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 du ring the selection of BM‐MSC donors for regen erative 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.