期刊
EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING
卷 48, 期 3, 页码 708-720出版社
SPRINGER
DOI: 10.1007/s00259-020-05087-0
关键词
Stem cells; CRISPR; Cas 9; Molecular imaging; Myocardial infarction; Reporter gene
资金
- National Key Research and Development Program of China [2016YFA0100900]
- National Natural Science Foundation of China (NSFC) [81761148029, 81725009, 81900255]
- Fundamental Research Funds for the Central Universities [2020FZZX001-05]
The study demonstrated the establishment of a CRISPR/Cas9-mediated multimodality reporter gene imaging system that can determine the dynamics and function of TF-hUiCMs in myocardial infarction, which is helpful for investigating the application of stem cell therapy.
Purpose To investigate the post-transplantation behaviour and therapeutic efficacy of human urinary-induced pluripotent stem cell-derived cardiomyocytes (hUiCMs) in infarcted heart. Methods We used clustered regularly interspaced short palindromic repeats/CRISPR-associated nuclease 9 (CRISPR/Cas9) technology to integrate a triple-fusion (TF) reporter gene into the AAVS1 locus in human urine-derived hiPSCs (hUiPSCs) to generate TF-hUiPSCs that stably expressed monomeric red fluorescent protein for fluorescence imaging, firefly luciferase for bioluminescence imaging (BLI) and herpes simplex virus thymidine kinase for positron emission tomography (PET) imaging. Results Transplanted cardiomyocytes derived from TF-hUiPSCs (TF-hUiCMs) engrafted and proliferated in the infarcted heart as monitored by both BLI and PET imaging and significantly improved cardiac function. Under ischaemic conditions, TF-hUiCMs enhanced cardiomyocyte (CM) glucose metabolism and promoted angiogenic activity. Conclusion This study established a CRISPR/Cas9-mediated multimodality reporter gene imaging system that can determine the dynamics and function of TF-hUiCMs in myocardial infarction, which is helpful for investigating the application of stem cell therapy.
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