Engineered heart tissue graft derived from somatic cell nuclear transferred embryonic stem cells improve myocardial performance in infarcted rat heart.
The concept of regenerating diseased myocardium by implanting engineered heart tissue (EHT) is intriguing. Yet it was limited by immune rejection and difficulties to be generated at a size with contractile properties. Somatic cell nuclear transfer is proposed as a practical strategy for generating autologous histocompatible stem (nuclear transferred embryonic stem [NT-ES]) cells to treat diseases. Nevertheless, it is controversial as NT-ES cells may pose risks in their therapeutic application. EHT from NT-ES cell-derived cardiomyocytes was generated through a series of improved techniques in a self-made mould to keep the EHTs from contraction and provide static stretch simultaneously. After 7 days of static and mechanical stretching, respectively, the EHTs were implanted to the infarcted rat heart. Four weeks after transplantation, the suitability of EHT in heart muscle repair after myocardial infarction was evaluated by histological examination, echocardiography and multielectrode array measurement. The results showed that large (thickness/diameter, 2-4 mm/10 mm) spontaneously contracting EHTs was generated successfully. The EHTs, which were derived from NT-ES cells, inte grated and electrically coupled to host myocardium and exerted beneficial effects on the left ventricular function of infarcted rat heart. No teratoma formation was observed in the rat heart implanted with EHTs for 4 weeks. NT-ES cells can be used as a source of seeding cells for cardiac tissue engineering. Large contractile EHT grafts can be constructed in vitro with the ability to survive after implantation and improve myocardial performance of infarcted rat hearts.
Lü
Shuanghong
S
Department of Tissue Engineering, Institute of Basic Medical Sciences and Tissue Engineering Research Center, Academy of Military Medical Sciences, Beijing, China Laboratory of Oncology, Affiliated Hospital of Academy of Military Medical Sciences, Beijing, China.
Li
Ying
Y
Gao
Shaorong
S
Liu
Sheng
S
Wang
Haibin
H
He
Wenjun
W
Zhou
Jin
J
Liu
Zhiqiang
Z
Zhang
Ye
Y
Lin
Qiuxia
Q
Duan
Cumi
C
Yang
Xiangzhong Jerry
XJ
Wang
Changyong
C
D000818:Animals; D053595:Embryonic Stem Cells / Q000166:cytology*; D006321:Heart / Q000502:physiology; D051379:Mice; D009200:Myocardial Contraction; D009203:Myocardial Infarction / Q000601:surgery*; D032383:Myocytes, Cardiac / Q000502:physiology*; D053652:Nuclear Transfer Techniques; D051381:Rats; D012038:Regeneration; D023822:Tissue Engineering / Q000379:methods*; D016378:Tissue Transplantation; D014182:Transplantation, Autologous