Persistence of intramyocardially transplanted murine induced pluripotent stem cell-derived cardiomyocytes from different developmental stages

被引：10

作者：

Peinkofer, Gabriel ^{[1
,2
,3
]}

Maass, Martina ^{[1
,4
,5
]}

Pfannkuche, Kurt ^{[2
,3
,6
,7
]}

Sachinidis, Agapios ^{[2
,7
]}

Baldus, Stephan ^{[1
]}

Hescheler, Juergen ^{[2
]}

Saric, Tomo ^{[2
]}

Halbach, Marcel ^{[1
]}

机构：

[1] Univ Hosp Cologne, Dept Internal Med 3, Cologne, Germany

[2] Univ Cologne, Med Fac, Inst Neurophysiol, Ctr Physiol & Pathophysiol, Robert Koch Str 37, D-50931 Cologne, Germany

[3] Univ Cologne, Marga & Walter Boll Lab Cardiac Tissue Engn, Cologne, Germany

[4] Univ Cologne, Dept Ophthalmol, Med Fac, Cologne, Germany

[5] Univ Cologne, Ocular GvHD Competence Ctr PS, Med Fac, Cologne, Germany

[6] Univ Hosp Cologne, Dept Pediat Cardiol, Cologne, Germany

[7] Univ Cologne, Ctr Mol Med, Cologne, Germany

来源：

STEM CELL RESEARCH & THERAPY | 2021年 / 12卷 / 01期

关键词：

Induced pluripotent stem cell-derived cardiomyocytes; Cell therapy; Cell persistence;

D O I：

10.1186/s13287-020-02089-5

中图分类号：

Q813 [细胞工程];

学科分类号：

摘要：

Background Induced pluripotent stem cell-derived cardiomyocytes (iPSC-CM) are regarded as promising cell type for cardiac cell replacement therapy, but it is not known whether the developmental stage influences their persistence and functional integration in the host tissue, which are crucial for a long-term therapeutic benefit. To investigate this, we first tested the cell adhesion capability of murine iPSC-CM in vitro at three different time points during the differentiation process and then examined cell persistence and quality of electrical integration in the infarcted myocardium in vivo. Methods To test cell adhesion capabilities in vitro, iPSC-CM were seeded on fibronectin-coated cell culture dishes and decellularized ventricular extracellular matrix (ECM) scaffolds. After fixed periods of time, stably attached cells were quantified. For in vivo experiments, murine iPSC-CM expressing enhanced green fluorescent protein was injected into infarcted hearts of adult mice. After 6-7 days, viable ventricular tissue slices were prepared to enable action potential (AP) recordings in transplanted iPSC-CM and surrounding host cardiomyocytes. Afterwards, slices were lysed, and genomic DNA was prepared, which was then used for quantitative real-time PCR to evaluate grafted iPSC-CM count. Results The in vitro results indicated differences in cell adhesion capabilities between day 14, day 16, and day 18 iPSC-CM with day 14 iPSC-CM showing the largest number of attached cells on ECM scaffolds. After intramyocardial injection, day 14 iPSC-CM showed a significant higher cell count compared to day 16 iPSC-CM. AP measurements revealed no significant difference in the quality of electrical integration and only minor differences in AP properties between d14 and d16 iPSC-CM. Conclusion The results of the present study demonstrate that the developmental stage at the time of transplantation is crucial for the persistence of transplanted iPSC-CM. iPSC-CM at day 14 of differentiation showed the highest persistence after transplantation in vivo, which may be explained by a higher capability to adhere to the extracellular matrix.

引用

页数：13

共 55 条

[21] Identification of Thalidomide-Specific Transcriptomics and Proteomics Signatures during Differentiation of Human Embryonic Stem Cells [J].