Law Peter K, Haider Kh, Fang G, Jiang S, Chua F, Lim Y T, Sim E
Cell Therapy Research Foundation, Memphis, TN, USA.
Mol Cell Biochem. 2004 Aug;263(1-2):173-8.
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.
心脏再生的生物工程学方法可能为心力衰竭提供一种新的治疗手段。2002年5月14日，一名55岁的缺血性心肌梗死患者在冠状动脉搭桥术后，接受了25次注射，共向其心肌内注入了4.65亿个由环磷酸鸟苷（cGMP）产生的纯成肌细胞。到2002年8月28日，他的心电图正常，未显示心律失常。他的射血分数增加了13%。他不再像治疗前那样感到呼吸急促和心绞痛。利用环孢素作为免疫抑制剂，通过17个人/猪异种移植阐明了三种肌生成机制。一些成肌细胞发育成为心肌细胞。其他一些成肌细胞则通过自然细胞融合将其细胞核转移到宿主心肌细胞中。还有一些成肌细胞与卫星细胞一起形成骨骼肌纤维。收缩细丝的重新产生增强了心脏的收缩力。用血管内皮生长因子165（VEGF165）基因转导的人成肌细胞在猪心肌中产生的毛细血管比安慰剂组多六倍。尽管在6周时停用了环孢素，但在长达20周的时间内未观察到异种移植排斥反应。比较了自体移植与同种异体移植的优缺点，以指导心脏细胞治疗的未来发展。
