The objective of the current study is to develop a new method for tracking transplanted human induced pluripotent stem cells‐derived cardiomyocytes (hiPSC‐CMs) using magnetic resonance imaging (MRI). The CRISPR/dCas9 activation system is employed to overexpress ferritin heavy chain (FHC) in hiPSC‐CMs. The mRNA and protein expression of FHC in hiPSC and hiPSC‐CMs significantly increased after transfection. Iron chloride does not affect the cell viability in a concentration range from 0 to 2000 µm. hiPSCs overexpressing FHC (hiPSC‐ FHCOE) and hiPSC‐CMs overexpressing FHC (hiPSC‐CM‐FHCOE) significantly enhanced cellular uptake of iron chloride but with no changes in electrophysiological properties compared to hiPSC‐CM‐Control. Furthermore, hiPSC‐CM‐FHCOE presented robust contrast and lower T2* values, signifying their potential as highly effective candidates for cardiac MRI. Next, hiPSC‐CM‐FHCOE is injected into mouse hearts and after 3 days of transplantation, MR images are obtained. hiPSC‐CM‐FHCOE cells exhibited clear signals in the hearts with lower T2* and rapid signal decay. Collectively, data from this proof‐of‐concept study demonstrated that endogenous labeling with FHC in hiPSC‐CMs can be a potent strategy for enhancing the accuracy of cardiac MRI. This technology represents a significant step forward in tracking the transplanted hiPSC‐CMs in the hearts of live animals.

中文翻译：

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表达磁共振成像报告基因的人类诱导多能干细胞系的产生

当前研究的目的是开发一种使用磁共振成像（MRI）追踪移植的人类诱导多能干细胞衍生心肌细胞（hiPSC-CM）的新方法。 CRISPR/dCas9 激活系统用于在 hiPSC-CM 中过表达铁蛋白重链 (FHC)。转染后 hiPSC 和 hiPSC-CM 中 FHC 的 mRNA 和蛋白表达显着增加。氯化铁在 0 至 2000 µ 浓度范围内不影响细胞活力米。 hiPSC 过表达 FHC（hiPSC-FHCOE）和过度表达 FHC 的 hiPSC-CM（hiPSC-CM-FHCOE）与 hiPSC-CM-Control 相比，细胞对氯化铁的摄取显着增强，但电生理特性没有变化。此外，hiPSC-CM-FHCOE呈现出强大的对比度和较低的 T2* 值，表明它们作为心脏 MRI 高效候选者的潜力。接下来，hiPSC-CM-FHCOE将其注射到小鼠心脏中，移植3天后，获得MR图像。 hiPSC-CM-FHCOE细胞在 T 值较低的心脏中表现出清晰的信号2* 和快速信号衰减。总的来说，这项概念验证研究的数据表明，在 hiPSC-CM 中使用 FHC 进行内源标记可以成为提高心脏 MRI 准确性的有效策略。这项技术代表着在追踪活体动物心脏中移植的 hiPSC-CM 方面向前迈出了重要一步。