Multimodality molecular imaging to monitor transplanted stem cells for the treatment of ischemic heart disease

Zhijun Pei; Xiaoli Lan; Zhen Cheng; Chunxia Qin; Xiaotian Xia; Hui Yuan; Zhiling Ding; Yongxue Zhang

doi:10.1371/journal.pone.0090543

Multimodality molecular imaging to monitor transplanted stem cells for the treatment of ischemic heart disease

PLoS One. 2014 Mar 7;9(3):e90543. doi: 10.1371/journal.pone.0090543. eCollection 2014.

Authors

Zhijun Pei¹, Xiaoli Lan², Zhen Cheng³, Chunxia Qin², Xiaotian Xia², Hui Yuan², Zhiling Ding², Yongxue Zhang²

Affiliations

¹ Department of Nuclear Medicine, Union Hospital, Tongji Medical College of Huazhong University of Science and Technology, Hubei Province Key Laboratory of Molecular Imaging, Wuhan, China; Department of PET Center, Taihe Hospital, Hubei University of Medicine, Shiyan City, Hubei Province, China.
² Department of Nuclear Medicine, Union Hospital, Tongji Medical College of Huazhong University of Science and Technology, Hubei Province Key Laboratory of Molecular Imaging, Wuhan, China.
³ Molecular Imaging Program at Stanford and Bio-X Program, Stanford University, Stanford, California, United States of America.

Abstract

Purpose: Non-invasive techniques to monitor the survival and migration of transplanted stem cells in real-time is crucial for the success of stem cell therapy. The aim of this study was to explore multimodality molecular imaging to monitor transplanted stem cells with a triple-fused reporter gene [TGF; herpes simplex virus type 1 thymidine kinase (HSV1-tk), enhanced green fluorescence protein (eGFP), and firefly luciferase (FLuc)] in acute myocardial infarction rat models.

Methods: Rat myocardial infarction was established by ligating the left anterior descending coronary artery. A recombinant adenovirus carrying TGF (Ad5-TGF) was constructed. After transfection with Ad5-TGF, 5 × 10(6) bone marrow mesenchymal stem cells (BMSCs) were transplanted into the anterior wall of the left ventricle (n = 14). Untransfected BMSCs were as controls (n = 8). MicroPET/CT, fluorescence and bioluminescence imaging were performed. Continuous images were obtained at day 2, 3 and 7 after transplantation with all three imaging modalities and additional images were performed with bioluminescence imaging until day 15 after transplantation.

Results: High signals in the heart area were observed using microPET/CT, fluorescence and bioluminescence imaging of infarcted rats injected with Ad5-TGF-transfected BMSCs, whereas no signals were observed in controls. Semi-quantitative analysis showed the gradual decrease of signals in all three imaging modalities with time. Immunohistochemistry assays confirmed the location of the TGF protein expression was the same as the site of stem cell-specific marker expression, suggesting that TGF tracked the stem cells in situ.

Conclusions: We demonstrated that TGF could be used as a reporter gene to monitor stem cells in a myocardial infarction model by multimodality molecular imaging.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Immunohistochemistry
Molecular Imaging / methods*
Multimodal Imaging / methods*
Myocardial Ischemia / therapy*
Polymerase Chain Reaction
Rats
Rats, Sprague-Dawley
Stem Cell Transplantation / methods*

Grants and funding

This study was supported by the National Natural Science Foundation of China (No. 30830041, 30571816, 30772208, and 30970853) (http://www.nsfc.gov.cn/Portal0/default152.htm), the China Postdoctoral Science Foundation (2005037194) (http://211.166.12.38/V1/Program1/Default.aspx), and Hubei Province Science Fund for Distinguished Young Scholars (2010CDA094) (http://www.hbstd.gov.cn/). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.