Thymosin beta-4 improves endothelial function and reparative potency of diabetic endothelial cells differentiated from patient induced pluripotent stem cells.
Stem Cell Res Ther
; 13(1): 13, 2022 01 10.
Article
em En
| MEDLINE
| ID: mdl-35012642
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 ß-4 (Tb-4) on endothelial function using dia-hiPSC-ECs as disease model of endothelial dysfunction. METHODS ANDRESULTS:
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.Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Timosina
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Diabetes Mellitus Tipo 2
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Células-Tronco Pluripotentes Induzidas
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Stem Cell Res Ther
Ano de publicação:
2022
Tipo de documento:
Article
País de afiliação:
Singapura