Thymosin beta-4 improves endothelial function and reparative potency of diabetic endothelial cells differentiated from patient induced pluripotent stem cells

  • Stem Cell Res Ther. 2022 Jan 10;13(1):13. doi: 10.1186/s13287-021-02687-x.
Liping Su  1 ,  Xiaocen Kong  2 ,  Szejie Loo  1 ,  Yu Gao  3 ,  Bingli Liu  2 ,  Xiaofei Su  2 ,  Rinkoo Dalan  4 ,  Jianhua Ma  5 ,  Lei Ye  6
Affiliations
  • 1. National Heart Research Institute Singapore, National Heart Centre Singapore, Singapore, 169609, Singapore.
  • 2. Department of Endocrinology, Nanjing First Hospital, Nanjing Medical University, Nanjing, 210029, China.
  • 3. Department of Cardiology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200127, China.
  • 4. Department of Endocrinology, Tan Tock Seng Hospital, Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, Singapore.
  • 5. Department of Endocrinology, Nanjing First Hospital, Nanjing Medical University, Nanjing, 210029, China. [email protected].
  • 6. National Heart Research Institute Singapore, National Heart Centre Singapore, Singapore, 169609, Singapore. [email protected].
PMID: 35012642 DOI: 10.1186/s13287-021-02687-x
Abstract

Background: Prior studies show that signature phenotypes of diabetic human induced pluripotent stem cells derived endothelial cells (dia-hiPSC-ECs) are disrupted glycine homeostasis, increased senescence, impaired mitochondrial function and angiogenic potential as compared with healthy hiPSC-ECs. In the current study, we aimed to assess the role of thymosin β-4 (Tb-4) on endothelial function using dia-hiPSC-ECs as disease model of endothelial dysfunction.

Methods and results: Using dia-hiPSC-ECs as models of endothelial dysfunction, we determined the effect of Tb-4 on cell proliferation, senescence, cyto-protection, protein expression of intercellular adhesion molecule-1 (ICAM-1), secretion of endothelin-1 and MMP-1, mitochondrial membrane potential, and cyto-protection in vitro and angiogenic potential for treatment of ischemic limb disease in a mouse model of type 2 diabetes mellitus (T2DM) in vivo. We found that 600 ng/mL Tb4 significantly up-regulated Akt activity and Bcl-xL protein expression, enhanced dia-hiPSC-EC viability and proliferation, limited senescence, reduced endothelin-1 and MMP-1 secretion, and improved reparative potency of dia-hiPSC-ECs for treatment of ischemic limb disease in mice with T2DM. However, Tb4 had no effect on improving mitochondrial membrane potential and glycine homeostasis and reducing intercellular adhesion molecule-1 protein expression in dia-hiPSC-ECs.

Conclusions: Tb-4 improves endothelial dysfunction through enhancing hiPSC-EC viability, reducing senescence and endothelin-1 production, and improves angiogenic potency in diabetes.

Keywords
Endothelial function; Endothelium; Mitochondrial function; Senescence; Thymosin.
Products