心血管疾病高居我国致死病因首位，并还在持续上升，其中心肌梗死引起心肌细胞丢失导致的心力衰竭是心血管病总死亡率上升的主要原因。现有治疗难以逆转心梗后心衰进程，因此如何减少心梗后心肌细胞丢失、促进功能重建是制约心衰发生发展、降低心梗死亡率的关键环节，也是生命医学领域亟须解决的重大科学问题。
近日，来自中国科学院上海生命科学研究院杨黄恬研究组与浙江大学医学院附属第二医院王建安、胡新央团队合作揭示了人胚胎干细胞（human embryonic stem cells，hESCs）衍生的心血管前体细胞（cardiovascular precursor cells，CVPCs）移植对非人灵长类心梗模型的心脏保护作用。该研究开展了国际上首个NHP心血管领域的大样本研究，在NHP急性心梗模型移植hPSC-CVPCs的实验过程中比较了单用环孢霉素以及环孢霉素、甲泼尼龙和CD25抗体舒莱组合（multiple-drug regimen，MDR）的免疫抑制方案对移植细胞存活、安全性等的影响。结果表明，MDR实验组中移植细胞的驻留率和存活率显著高于单用环孢霉素组，但即使在MDR组中，移植后140天也未检测到移植细胞。有意思的是，MDR+细胞移植组与无细胞移植组相比，心梗后内源性心肌细胞凋亡减少，左室心功能改善。此外，MDR组及MDR+hPSC-CVPCs组移植动物心脏中T淋巴细胞浸润明显少于心梗组，而单用环孢菌素处理则不能有效降低受体心脏对移植细胞的排斥反应。该研究为干细胞的转化研究提供了重要数据，并提示旁分泌效应在hPSC-CVPCs心肌保护作用中可能发挥重要作用。
该研究进一步证实了包括人胚胎干细胞和人诱导多能干细胞在内的人多能干细胞在再生医学应用上具有重要前景，但在开展临床试验前还需要在大型动物模型中进行更深入的安全性和有效性评价，期间也须进行免疫抑制疗法的开发，以有序推进干细胞疗法治疗心脏疾病的临床应用。
推荐阅读原文：
Lack of Remuscularization Following Transplantation of Human Embryonic Stem Cell-Derived Cardiovascular Progenitor Cells in Infarcted Nonhuman Primates.
Human pluripotent stem cell-derived cardiovascular progenitor cells (hPSC-CVPCs) should be thoroughly investigated in large animal studies before testing in clinical trials. To clarify if hPSC-CVPCs can engraft for long time in the heart of primates after myocardial infarction (MI) and compare the effectiveness and safety of immunosuppression with cyclosporine alone or multiple-drug regimen (MDR) containing cyclosporine, methylprednisolone, and simulect in cynomolgous monkeys that had received intramyocardial injections of 1×
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EGFP-expressing hPSC-CVPCs after MI. A third group of animals received the immunosuppression MDR but without cell therapy after MI (MI+MDR group). Measurements of EGFP gene levels and EGFP immunofluorescence staining indicated that the hPSC-CVPC engraftment rate was greater in the MI+MDR+CVPC group than that in the MI+Cyclosporine+CVPC group. However, even in the MI+MDR+CVPC group, no transplanted cells could be detected at 140 days after transplantation. Concomitantly, immunofluorescent analysis of CD3, CD4, and CD8 expression indicated that T lymphocyte infiltration in the CVPC-transplanted hearts was less in the MDR-treated animals than in the cyclosporine alone-treated animals. The recovery of left-ventricular (LV) function at day 28 post-MI in the MI+MDR+CVPC group was better than that in the MI+MDR group. Apoptotic cardiac cells were also less common in the MI+MDR+CVPC group than in the MI+MDR group, while both immunosuppression regimens were associated with transient hepatic dysfunction. This is the largest study of hPSCs in non-human primates in cardiovascular field so far (n=32). Compared to cyclosporine alone, MDR attenuates immune rejection and improves survival of hPSC-CVPCs in primates; this is associated with less apoptosis of native cardiac cells and better recovery of LV function at 28 days. However, even with MDR, transplanted hPSC-CVPCs do not engraft and do not survive at 140 days after transplantation, thereby excluding remuscularization as a mechanism for the functional effect.
