Hetrombopag, a Thrombopoietin Receptor Agonist, Protects Cardiomyocyte Survival from Oxidative Stress Damage as an Enhancer of Stem Cells
作者
Zhou, NN;Wang, JC;Li, XD;Zhao, Y;Sun, YY;Zou, CW
作者单位
[Zhou, Nannan; Wang, Jianchun; Li, Xiaodong; Zhao, Yong; Sun, Yuanyuan] Shandong Univ, Shandong Prov Hosp, Dept Geriatr Cardiol, Jinan, Peoples R China.;-;[Zou, Chengwei] Shandong Univ, Shandong Prov Hosp, Dept Cardiovasc Surg, Jinan, Peoples R China.
摘要
Current human umbilical cord blood stem cell therapy faces the great challenges, because the stem cells are scarce and cannot survive for a long time. Here we describe how hetrombopag, an orally-active TPO receptor agonists, enhanced ex vivo expansion of human UCB stem cells, and protected cardiac myocytes from the damage caused by oxidative stress.;-;Ex vivo expansion of stem cells were performed in serum-free medium supplemented with rhSCF and rhFL plus hetrombopag for 7 days. The percentage and number of stem cell subsets were determined by flow cytometry. Rat cardiac myocytes, ex vivo expanded stem cells, or cardiac myocytes plus ex vivo expanded stem cells were serum starved for 24 hours, and were then subjected to H2O2, hetrombopag or both for 12 hours at the indicated concentrations. Cell viability assays, protein microarrays and western blots were then performed in each group.;-;Our studies first revealed that the combination of hetrombopag and rhTPO manifested additive effect on ex vivo expansion of human UCB stem cells. Besides, hetrombopag dose-dependently enhanced the beneficial effects of ex vivo expanded human UCB MNCs in increasing the survival of injured cardiomyocytes during free oxygen radical stress.;-;These data, for the first time, uncovered a novel function of non-peptide small molecular TPO receptor agonists as enhancers of stem cells in protecting cardiac myocyte survival from oxidative stress damage, which might provide a new therapeutic avenue for the treatment of oxidative stress-related cardiovascular disease.
关键词
UMBILICAL-CORD BLOOD; ACUTE MYOCARDIAL-INFARCTION; MONONUCLEAR-CELLS; ADULT RECIPIENTS; AKR-501 YM477; TRANSPLANTATION; ELTROMBOPAG; HEMATOPOIESIS; AKT; EXPANSION
基本信息
