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利用人甲状腺钠碘转运体报告基因成像对多层细胞片进行时空追踪：心肌梗死后大鼠模型的临床前研究。

Spatial and temporal tracking of multi-layered cells sheet using reporter gene imaging with human sodium iodide symporter: a preclinical study using a rat model of myocardial infarction.

机构信息

Department of Molecular Pharmacology, National Cerebral and Cardiovascular Center Research Institute, Osaka, Japan.

Graduate School of Science and Technology, Hirosaki University, Aomori, Japan.

出版信息

Eur J Nucl Med Mol Imaging. 2024 Dec;52(1):74-87. doi: 10.1007/s00259-024-06889-2. Epub 2024 Aug 29.

DOI:10.1007/s00259-024-06889-2
PMID:39207487
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11599416/
Abstract

PURPOSE

This study aimed to evaluate a novel technique for cell tracking by visualising the activity of the human sodium/iodide symporter (hNIS) after transplantation of hNIS-expressing multilayered cell sheets in a rat model of chronic myocardial infarction.

METHODS

Triple-layered cell sheets were generated from mouse embryonic fibroblasts (MEFs) derived from mice overexpressing hNIS (hNIS-Tg). Myocardial infarction was induced by permanent ligation of the left anterior descending coronary artery in F344 athymic rats, and a triple-layered MEFs sheets were transplanted to the infarcted area two weeks after surgery. To validate the temporal tracking and kinetic analysis of the transplanted MEFs sheets, sequential cardiac single-photon emission computed tomography (SPECT) examinations with a TcO injection were performed. The cell sheets generated using MEFs of wild-type mice (WT) served as controls.

RESULTS

A significantly higher amount of TcO was taken into the hNIS-Tg MEFs than into WT MEFs (146.1 ± 30.9-fold). The obvious accumulation of TcO was observed in agreement with the region where hNIS-Tg MEFs were transplanted, and these radioactivities peaked 40-60 min after TcO administration. The volume of distribution of the hNIS-Tg MEF sheets declined gradually after transplantation, implying cellular malfunction and a loss in the number of transplanted cells.

CONCLUSION

The reporter gene imaging with hNIS enables the serial tracking and quantitative kinetic analysis of cell sheets transplanted to infarcted hearts.

摘要

目的

本研究旨在评估一种通过可视化人钠/碘同向转运体（hNIS）活性来追踪细胞的新技术，该技术用于将 hNIS 表达的多层细胞片在慢性心肌梗死大鼠模型中移植。

方法

采用转染 hNIS 的小鼠胚胎成纤维细胞（MEF）（hNIS-Tg）构建三层细胞片。通过结扎 F344 无胸腺大鼠的左前降支冠状动脉诱导心肌梗死，在手术后两周将三层 MEF 细胞片移植到梗死区。为了验证移植的 MEF 细胞片的时间追踪和动力学分析，进行了 TcO 注射的连续心脏单光子发射计算机断层扫描（SPECT）检查。使用野生型小鼠（WT）的 MEF 生成的细胞片作为对照。

结果

hNIS-Tg MEF 摄取的 TcO 明显多于 WT MEF（146.1±30.9 倍）。在 hNIS-Tg MEF 移植的区域观察到明显的 TcO 积聚，这些放射性活性在 TcO 给药后 40-60 分钟达到峰值。hNIS-Tg MEF 片的分布容积在移植后逐渐下降，表明细胞功能障碍和移植细胞数量减少。

结论

hNIS 的报告基因成像可对移植到梗死心脏的细胞片进行连续追踪和定量动力学分析。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3c74/11599416/32a834b0ead6/259_2024_6889_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3c74/11599416/e093e7638a47/259_2024_6889_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3c74/11599416/22884da97ed5/259_2024_6889_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3c74/11599416/3962cc94e168/259_2024_6889_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3c74/11599416/ac2ca72aaf59/259_2024_6889_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3c74/11599416/800e0ed09c18/259_2024_6889_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3c74/11599416/32a834b0ead6/259_2024_6889_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3c74/11599416/e093e7638a47/259_2024_6889_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3c74/11599416/22884da97ed5/259_2024_6889_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3c74/11599416/3962cc94e168/259_2024_6889_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3c74/11599416/ac2ca72aaf59/259_2024_6889_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3c74/11599416/800e0ed09c18/259_2024_6889_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3c74/11599416/32a834b0ead6/259_2024_6889_Fig6_HTML.jpg

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