利用成人心肌成纤维细胞诱导生成的多能干细胞衍生和高效植入患者特异性心肌细胞片。
Derivation and high engraftment of patient-specific cardiomyocyte sheet using induced pluripotent stem cells generated from adult cardiac fibroblast.
机构信息
From the Cardiovascular Division, Department of Medicine (L.Z., J.G., P.Z., Q.X., S.S.R., J.Z.), Department of Integrative Biology and Physiology, School of Medicine (S.C.W., T.D.O.C.), Stem Cell Institute and Department of Pediatrics (L.X., J.T., M.K.), and Department of Surgery (K.L.), University of Minnesota, Minneapolis, MN; and Department of Cardiology, First Affiliated Hospital, Nanjing Medical University, Nanjing, China (J.G.).
出版信息
Circ Heart Fail. 2015 Jan;8(1):156-66. doi: 10.1161/CIRCHEARTFAILURE.114.001317. Epub 2014 Nov 24.
BACKGROUND
Induced pluripotent stem cells (iPSCs) can be differentiated into potentially unlimited lineages of cell types for use in autologous cell therapy. However, the efficiency of the differentiation procedure and subsequent function of the iPSC-derived cells may be influenced by epigenetic factors that the iPSCs retain from their tissues of origin; thus, iPSC-derived cells may be more effective for treatment of myocardial injury if the iPSCs were engineered from cardiac-lineage cells, rather than dermal fibroblasts.
METHODS AND RESULTS
We show that human cardiac iPSCs (hciPSCs) can be generated from cardiac fibroblasts and subsequently differentiated into exceptionally pure (>92%) sheets of cardiomyocytes (CMs). The hciPSCs passed through all the normal stages of differentiation before assuming a CM identity. When using the fibrin gel-enhanced delivery of hciPSC-CM sheets at the site of injury in infarcted mouse hearts, the engraftment rate was 31.91%±5.75% at Day 28 post transplantation. The hciPSC-CM in the sheet also appeared to develop a more mature, structurally aligned phenotype 28 days after transplantation and was associated with significant improvements in cardiac function, vascularity, and reduction in apoptosis.
CONCLUSIONS
These data strongly support the potential of hciPSC-CM sheet transplantation for the treatment of heart with acute myocardial infarction.
背景
诱导多能干细胞（iPSCs）可分化为具有潜在用途的自体细胞疗法的细胞类型。然而，分化程序的效率和 iPSC 衍生细胞的后续功能可能会受到 iPSCs 从其组织来源中保留的表观遗传因素的影响；因此，如果 iPSC 是从心脏谱系细胞而不是皮肤成纤维细胞中构建的，那么 iPSC 衍生的细胞可能对心肌损伤的治疗更有效。
方法和结果
我们证明了可以从心脏成纤维细胞生成人心诱导多能干细胞（hciPSCs），并随后将其分化为非常纯净的（>92%）心肌细胞（CM）片。 hciPSCs 在获得 CM 身份之前经历了所有正常的分化阶段。在使用纤维蛋白凝胶增强移植到梗塞的小鼠心脏损伤部位的 hciPSC-CM 片的方法中，在移植后第 28 天的植入率为 31.91%±5.75%。移植后 28 天，CM 片中的 hciPSC-CM 似乎也发展出更成熟、结构排列的表型，并与心脏功能、血管生成和细胞凋亡减少的显著改善相关。
结论
这些数据强烈支持 hciPSC-CM 片移植治疗急性心肌梗死心脏的潜力。
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