Noninvasive Quantification and Optimization of Acute Cell Retention by In Vivo Positron Emission Tomography After Intramyocardial Cardiac-Derived Stem Cell Delivery

Objectives The aim of this study was to quantify acute myocardial retention of cardiac-derived stem cells (CDCs) and evaluate different delivery methods with positron emission tomography (PET). Background Success of stem cell transplantation for cardiac regeneration is partially limited by low reten...

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Published in:	Journal of the American College of Cardiology 2009-10, Vol.54 (17), p.1619-1626
Main Authors:	Terrovitis, John, MD, Lautamäki, Riikka, MD, PhD, Bonios, Michael, MD, Fox, James, BS, Engles, James M., MS, MBA, Yu, Jianhua, BS, Leppo, Michelle K., BS, Pomper, Martin G., MD, PhD, Wahl, Richard L., MD, Seidel, Jurgen, PhD, Tsui, Benjamin M., PhD, Bengel, Frank M., MD, Abraham, M. Roselle, MD, Marbán, Eduardo, MD, PhD
Format:	Article
Language:	eng
Subjects:	Acquisitions & mergers adenosine Animals Biological and medical sciences cardiac stem cells Cardiology. Vascular system Cardiovascular Cell Survival Coronary Vessels - surgery Delivery. Postpartum. Lactation Female fibrin glue Glucose Gynecology. Andrology. Obstetrics Heart - physiology Heart rate Histology Internal Medicine Labeling Ligation Male Medical sciences Methods Models, Animal Myocardial Ischemia - therapy Myocardium Myocytes, Cardiac - transplantation Optimization Ostomy PET Positron-Emission Tomography Rats Rats, Inbred WKY Regeneration Retention Rodents Stem Cell Transplantation - methods Stem cells Studies
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Summary:	Objectives The aim of this study was to quantify acute myocardial retention of cardiac-derived stem cells (CDCs) and evaluate different delivery methods with positron emission tomography (PET). Background Success of stem cell transplantation for cardiac regeneration is partially limited by low retention/engraftment of the delivered cells. A clinically applicable method for accurate quantification of cell retention would enable optimization of cell delivery. Methods The CDCs were derived from syngeneic, male Wistar Kyoto (WK) rats labeled with [18 F]-fluoro-deoxy-glucose (18 FDG) and injected intramyocardially into the ischemic region of female WK rats after permanent left coronary artery ligation. The effects of fibrin glue (FG), bradycardia (adenosine), and cardiac arrest were examined. Imaging with18 FDG PET was performed for quantification of cell retention. Quantitative polymerase chain reaction (PCR) for the male-specific SRY gene was performed to validate the PET results. Results Myocardial retention of cells suspended in phosphate-buffered saline 1 h after delivery was 17.6 ± 11.5% by PCR and 17.8 ± 7.3% by PET. When CDCs were injected immediately after induction of cardiac arrest, retention was increased to 75.6 ± 18.6%. Adenosine slowed the ventricular rate and doubled CDC retention (35.4 ± 5.3%). A similar increase in CDC retention was observed after epicardial application of FG at the injection site (37.5 ± 8.2%). The PCR revealed a significant increase in 3-week cell engraftment in the FG animals (22.1 ± 18.6% and 5.3 ± 3.1%, for FG and phosphate-buffered saline, respectively). Conclusions In vivo PET permits accurate measurement of CDC retention early after intramyocardial delivery. Sealing injection sites with FG or lowering ventricular rate by adenosine might be clinically translatable methods for improving stem cell engraftment in a beating heart.
ISSN:	0735-1097 1558-3597