Transplantation of parthenogenetic embryonic stem cells ameliorates cardiac dysfunction and remodeling after myocardial infarction
首发时间:2012-12-21
Abstract:Aims: Parthenogenetic embryonic stem cells (pESCs) are derived from artificially activated oocytes without fertilization and therefore raise minimal ethical concerns and may serve as attractive candidates for regenerative medicine. We thought to investigate whether pESCs can repair myocardial infarction (MI). Methods and Results: Mice (n=89) survived coronary ligation randomly received undifferentiated pESCs, ESCs, or saline. Sham-operated mice received no treatment (n=21). After 7 days, pESCs transplantation promoted pro-angiogenic factors secretion and reduced infiltrated leukocytes. pESCs-treated hearts, superior to ESC group, showed prevented cardiac remodeling and enhanced angiogenesis in and 30 days post MI. Heart contractile function was notably improved by administration of pESCs by 30 days. Moreover, tissues regenerated from the engrafted pESCs in the infarcted myocardium were positive for cardiomyocyte, endothelial cell and smooth muscle cell markers. Furthermore, teratoma fomation appeared in ESCs-treated mice in high proportion (6/34), but surprisingly not found in pESCs-treated mice (0/30) by 30 days. Conclusions: Cardiac dysfunction and adverse ventricular remodeling post MI were attenuated by pESCs transplantation, which may represent an effective and relatively safer strategy for autologous cell therapy in females.
keywords: Parthenogenetic stem cells embryonic stem cell myocardial infarction teratoma stem cell therapy
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孤雌胚胎干细胞移植缓解心肌梗死后心功能失常和室性重构
摘要:目的:孤雌胚胎干细胞(pESC)是胚胎干细胞的一种,免疫原性低且不受伦理限制,但尚无有关pESC移植治疗心肌梗死的研究报道。本实验将pESC和受精卵来源的ESC移植到缺血心肌,探索pESC移植治疗心梗的可行性和安全性。方法:本实验通过永久结扎小鼠左前降支冠脉致心肌梗死,立即将pESC或ESC注射到梗死周边区,盐水组只注射生理盐水,并设假手术组为正常功能对照组。设4个时间点,分析pESC对心肌梗死的疗效。结果:移植pESC能促进缺血区VEGFa、bFGF和IGF-1的表达,减少梗死区浸润的白细胞;植入细胞可表达心肌细胞、内皮细胞和平滑肌细胞标志分子;pESC移植能显著改善心脏功能,减小梗死范围,降低胶原沉积,增强梗死区血管密度;移植到30d时,只ESC移植在心脏部位生成较高比例(6/29)的畸胎瘤;然而移植90d时,pESC组有畸胎瘤发生(2/14)。结论:pESC可发挥旁分泌机制;pESC可再生心肌组织;移植pESC能显著改善心脏功能,有效抑制心室重构;pESC移植安全性较高,但长期移植仍有致畸胎瘤隐患。
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