1. Academic Validation
  2. Thymosin beta-4 improves endothelial function and reparative potency of diabetic endothelial cells differentiated from patient induced pluripotent stem cells

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

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].
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.

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