Cell Therapy Research Foundation, Memphis, TN, USA; Cell Transplants Singapore Pte. Ltd., Singapore.
National University Hospital, Singapore.
Mol Cell Biochem. 2004 Aug;263(1):173-8. doi: 10.1023/B:MCBI.0000041859.60354.f5.
Bioengineering the regenerative heart may provide a novel treatment for heart failure. On May 14, 2002, a 55-year-old man suffering from ischemic myocardial infarction received 25 injections carrying 465 million cGMP-produced pure myoblasts into his myocardium after coronary artery bypass grafting. As on August 28, 2002, his EKG was normal and showed no arrhythmia. His ejection fraction increased by 13%. He no longer experienced shortness of breath and angina as he did before the treatment. Three myogenesis mechanisms were elucidated with 17 human/porcine xenografts using cyclosporine as immunosuppressant. Some myoblasts developed to become cardiomyocytes. Others transferred their nuclei into host cardiomyocytes through natural cell fusion. As yet others formed skeletal myofibers with satellite cells. De novo production of contractile filaments augmented the heart contractility. Human myoblasts transduced with VEGF165 gene produced six times more capillaries in porcine myocardium than in placebo. Xenograft rejection was not observed for up to 20 weeks despite cyclosporine discontinuation at 6 weeks. Pros and cons of autografts vs. allografts are compared to guide future development of heart cell therapy. (Mol Cell Biochem 263: 173-178, 2004).
生物工程心脏再生可能为心力衰竭提供一种新的治疗方法。2002 年 5 月 14 日，一名 55 岁男性因缺血性心肌梗死，在冠状动脉搭桥术后接受了 25 次注射，共注射了 4.65 亿个 cGMP 产生的纯成肌细胞到他的心肌中。截至 2002 年 8 月 28 日，他的心电图正常，没有心律失常。他的射血分数增加了 13%。他不再像治疗前那样出现呼吸急促和心绞痛。使用环孢素作为免疫抑制剂，通过 17 个人/猪异种移植物阐明了三种成肌机制。一些成肌细胞发育成为心肌细胞。其他的通过自然细胞融合将其细胞核转移到宿主心肌细胞中。还有一些与卫星细胞形成骨骼肌纤维。新产生的收缩纤维增强了心脏的收缩力。转导 VEGF165 基因的人成肌细胞在猪心肌中产生的毛细血管比安慰剂多 6 倍。尽管在 6 周时停止使用环孢素，但在 20 周内没有观察到异种移植物排斥。比较自体移植物与同种异体移植物的优缺点，以指导未来的心脏细胞治疗的发展。（分子细胞生物化学 263: 173-178, 2004）。
