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.

Both the transplantation of somatic cell nuclear transfer- and fertilization-derived mouse embryonic stem cells with temperature-responsive chitosan hydrogel improve myocardial performance in infarcted rat hearts.

The transplantation of embryonic stem cells could improve cardiac function but was limited by immune rejection as well as low cell retention and survival within the ischemic tissues. The somatic cell nuclear transfer (SCNT) is practical to generate autologous histocompatible stem (nuclear-transferred embryonic stem [NTES]) cells for diseases, but NTES may be arguably unsafe for therapeutic application. The temperature-responsive chitosan hydrogel is a suitable matrix in cell transplantation. As the scaffold, chitosan hydrogel was coinjected with NTES cells into the left ventricular wall of rat infarction models. Detailed histological analysis and echocardiography were performed to determine the structure and functional consequences of transplantation. The myocardial performance in SCNT- and fertilization-derived mouse ES cell transplantation with chitosan hydrogel was also compared. The results showed that both the 24-h cell retention and 4-week graft size were significantly greater in the NTES + chitosan group than that of NTES + phosphate-buffered saline (PBS) group (p < 0.01). The NTES cells might differentiate into cardiomyocytes in vivo. The heart function improved significantly in the chitosan + NTES group (fractional shortening: 28.7% +/- 2.8%) compared with that of PBS + NTES group (fractional shortening: 25.2% +/- 2.9%) at 4 weeks after transplantation (p < 0.01). In addition, the arteriole/venule densities within the infarcted area improved significantly in the chitosan + NTES group (280 +/- 17/mm(2)) compared with that of PBS + NTES group (234 +/- 16/mm(2)) at 4 weeks after transplantation (p < 0.01). There was no difference in the myocardial performance in SCNT- and fertilization-derived mouse ES cell transplantation with chitosan hydrogel. The NTES cells with chitosan hydrogel have been proved to possess therapeutic potential to improve the function of infarcted heart. Thus the method of in situ injectable tissue engineering is promising clinically.