Electrophysiological integration and action potential properties of transplanted cardiomyocytes derived from induced pluripotent stem cells
Electrophysiological integration and action potential properties of transplanted cardiomyocytes derived from induced pluripotent stem cells
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DOI：
10.1093/cvr/cvt213
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发表时间：
2013-12-01
影响因子：
10.8
通讯作者：
Mueller-Ehmsen, Jochen
中科院分区：
文献类型：
--
作者：
Halbach, Marcel;Peinkofer, Gabriel;Mueller-Ehmsen, Jochen
诱导多能干细胞衍生的心肌细胞（iPSCM）被认为是心脏细胞替代治疗的有前途的细胞类型。我们研究了长期的电生理整合和成熟的移植iPSCM，这是必不可少的治疗benefit.Murine iPSCM表达增强的绿色荧光蛋白和嘌呤霉素抗性的-肌球蛋白重链启动子的控制下，纯化通过抗生素选择和注射到成年小鼠心脏。在612天、36周或68个月后，制备受体心脏的活切片。切片通过放置在宿主组织中的单极电极进行局灶性刺激，并在切片内的移植细胞和邻近宿主组织中用玻璃微电极记录细胞内动作电位（AP）。可在所有时间点证明移植iPSCM到受体心脏中的持久性和电整合。耦合的质量得到改善，如所示的最大刺激频率为5.77 0.54 Hz，在612天，8.98 0.38 Hz，在36周和10.82 1.07 Hz，在移植后68个月无传导阻滞。iPSCM的AP特性在移植后612天至68个月逐渐成熟，但仍与宿主AP存在显著差异，移植后iPSCM可长期存活并与宿主组织电整合，支持其作为细胞替代疗法的潜力。移植后612天至68个月，电整合的质量得到改善，并且有电生理成熟的迹象。然而，即使在68个月后，移植iPSCM的AP特性也不同于受体心肌细胞的AP特性。
Induced pluripotent stem cell-derived cardiomyocytes (iPSCM) are regarded as promising cell type for cardiac cell replacement therapy. We investigated long-term electrophysiological integration and maturation of transplanted iPSCM, which are essential for therapeutic benefit.Murine iPSCM expressing enhanced green fluorescent protein and a puromycin resistance under control of the -myosin heavy chain promoter were purified by antibiotic selection and injected into adult mouse hearts. After 612 days, 36 weeks, or 68 months, viable slices of recipient hearts were prepared. Slices were focally stimulated by a unipolar electrode placed in host tissue, and intracellular action potentials (APs) were recorded with glass microelectrodes in transplanted cells and neighbouring host tissue within the slices. Persistence and electrical integration of transplanted iPSCM into recipient hearts could be demonstrated at all time points. Quality of coupling improved, as indicated by a maximal stimulation frequency without conduction blocks of 5.77 0.54 Hz at 612 days, 8.98 0.38 Hz at 36 weeks and 10.82 1.07 Hz at 68 months after transplantation. AP properties of iPSCM became more mature from 612 days to 68 months after transplantation, but still differed significantly from those of host APs.Transplanted iPSCM can persist in the long term and integrate electrically into host tissue, supporting their potential for cell replacement therapy. Quality of electrical integration improves between 612 days and 68 months after transplantation, and there are signs of an electrophysiological maturation. However, even after 68 months, AP properties of transplanted iPSCM differ from those of recipient cardiomyocytes.