Extending the time window of mammalian heart regeneration by thymosin beta 4

Journal of Cellular and Molecular Medicine

Liu Rui¹  Nie Yu¹  Lian Hong¹  He Feng¹  Han Chunyong¹  Meng Jian¹  Zheng Zhe¹ 

[1] State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China

关键词: neonatal mouse;    EPDCs;    cardiac regeneration;    Tβ4;   

DOI  :  10.1111/jcmm.12421

来源: Wiley

【 摘 要 】

Abstract

Recent studies demonstrated that the heart of 1-day-old neonatal mice could regenerate, with Wt1⁺ EPDCs migrating into myocardial regions after partial surgical resection, but this capacity was lost by 7 days of age. By treatment with Tβ4 to maintain Wt1 expression and retain the migrating feature of EPDCs in neonatal mice, we explored the possibility of restoring the cardiac regeneration potential of mice. We intraperitoneally injected Tβ4 into 1-day-old mice on daily basis and then apical resection was performed on the mice 7 days later. Twenty one days after the resection, morphological analysis revealed that the Tβ4-treated mice regenerated the resected ventricular apex, while the mice in PBS control group developed significant fibrosis without apical regeneration. The Tβ4-treated mice had significantly better ventricular ejection fraction and fractional shortening than controls. During the process of regeneration, Wt1⁺ EPDCs migrated into myocardial region and some of them expressed Islet1 and the markers for mature cardiomyocytes, such as cTnT and SαA. These characteristics of Wt1⁺ EPDCs were also seen in the heart regeneration of mice subjected to apical resection 1 day after birth. Tβ4 has no essential effect on cell cycle activity as no disruption of actin filaments was observed in Tβ4-treated hearts. These results revealed that the cardiac regeneration potential of neonatal mice could be extended to the 7th post-natal day by Tβ4 and Wt1⁺ EPDCs mobilization might play an important role in the extension.

【 授权许可】

CC BY   
© 2014 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.