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Original Articles

Multimodality Evaluation of the Viability of Stem Cells Delivered Into Different Zones of Myocardial Infarction

Ta-Chuan Hung, MD^*; Yoriyasu Suzuki, MD^*; Takashi Urashima, MD; Anthony Caffarelli, MD; Grant Hoyt; Ahmad Y. Sheikh, MD; Alan C. Yeung, MD; Irving Weissman, MD; Robert C. Robbins, MD; Jeff M. Bulte, PhD and Phillip C. Yang, MD

From the Division of Cardiovascular Medicine (T.-C.H., P.C.Y.), Department of Pediatrics (T.U.), Department of Pathology and Stem Cell Institute (I.W.), and Department of Cardiothoracic Surgery (A.C., G.H., A.Y.S., R.C.R.); Stanford University, Stanford, Calif; Mackay Memorial Hospital and Mackay Medicine, Nursing and Management College, Taipei, Taiwan (T.-C.H.); and Department of Radiology (Division of MR Research), Biomedical Engineering, and Chemical and Biomolecular Engineering and Cellular Imaging Section/Vascular Biology Program, Institute for Cell Engineering, The Johns Hopkins University School of Medicine, Baltimore, Md (J.M.B.).

Correspondence to Phillip C. Yang, MD, Stanford University Medical Center, 300 Pasteur Dr, Room H-2157, Stanford, CA 94305-5233. E-mail pyang{at}cvmed.stanford.edu

Received January 22, 2008; accepted May 19, 2008.

Background— We tested the hypothesis that multimodality imaging of mouse embryonic stem cells (mESCs) provides accurate assessment of cellular location, viability, and restorative potential after transplantation into different zones of myocardial infarction.

Methods and Results— Mice underwent left anterior descending artery ligation followed by transplantation of dual-labeled mESCs with superparamagnetic iron oxide and luciferase via direct injection into 3 different zones of myocardial infarction: intra-infarction, peri-infarction, and normal (remote). One day after transplantation, magnetic resonance imaging enabled assessment of the precise anatomic locations of mESCs. Bioluminescence imaging allowed longitudinal analysis of cell viability through detection of luciferase activity. Subsequent evaluation of myocardial regeneration and functional restoration was performed by echocardiography and pressure–volume loop analysis. Using 16-segment analysis, we demonstrated precise localization of dual-labeled mESCs. A strong correlation between histology and magnetic resonance imaging was established (r=0.962, P=0.002). Bioluminescent imaging data demonstrated that cell viability in the remote group was significantly higher than in other groups. Echocardiography and pressure–volume loop analysis revealed improved functional restoration in animals treated with mESCs, although myocardial regeneration was not observed.

Conclusions— Multimodality evaluation of mESC engraftment in the heterogeneous tissue of myocardial infarction is possible. Magnetic resonance imaging demonstrated accurate anatomic localization of dual-labeled mESCs. Bioluminescent imaging enabled assessment of variable viability of mESCs transplanted into the infarcted myocardium. Echocardiography and pressure–volume loop analysis validated the restorative potential of mESCs. Although mESCs transplanted into the remote zone demonstrated the highest viability, precise delivery of mESCs into the peri-infarction region might be equally critical in restoring the injured myocardium.

Key Words: heart failure • myocardial infarction • magnetic resonance imaging • stem cells, embryonic

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CLINICAL PERSPECTIVE

*Drs Hung and Suzuki contributed equally to this study.