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

John Terrovitis; Riikka Lautamäki; Michael Bonios; James Fox; James M. Engles; Jianhua Yu; Michelle K. Leppo; Martin G. Pomper; Richard L. Wahl; Jurgen Seidel; Benjamin M. Tsui; Frank M. Bengel; M. Roselle Abraham; Eduardo Marbán

doi:10.1016/j.jacc.2009.04.097

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

John Terrovitis, Riikka Lautamäki, Michael Bonios, James Fox, James M. Engles, Jianhua Yu, Michelle K. Leppo, Martin G. Pomper, Richard L. Wahl, Jurgen Seidel, Benjamin M. Tsui, Frank M. Bengel, M. Roselle Abraham, Eduardo Marbán

School of Medicine

Research output: Contribution to journal › Article › peer-review

207 Scopus citations

Abstract

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 [¹⁸F]-fluoro-deoxy-glucose (¹⁸FDG) 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 with ¹⁸FDG 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.

Original language	English (US)
Pages (from-to)	1619-1626
Number of pages	8
Journal	Journal of the American College of Cardiology
Volume	54
Issue number	17
DOIs	https://doi.org/10.1016/j.jacc.2009.04.097
State	Published - Oct 20 2009

Keywords

PET
adenosine
cardiac stem cells
fibrin glue

ASJC Scopus subject areas

Cardiology and Cardiovascular Medicine

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10.1016/j.jacc.2009.04.097

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Terrovitis, J., Lautamäki, R., Bonios, M., Fox, J., Engles, J. M., Yu, J., Leppo, M. K., Pomper, M. G., Wahl, R. L., Seidel, J., Tsui, B. M., Bengel, F. M., Abraham, M. R., & Marbán, E. (2009). Noninvasive Quantification and Optimization of Acute Cell Retention by In Vivo Positron Emission Tomography After Intramyocardial Cardiac-Derived Stem Cell Delivery. Journal of the American College of Cardiology, 54(17), 1619-1626. https://doi.org/10.1016/j.jacc.2009.04.097

Noninvasive Quantification and Optimization of Acute Cell Retention by In Vivo Positron Emission Tomography After Intramyocardial Cardiac-Derived Stem Cell Delivery. / Terrovitis, John; Lautamäki, Riikka; Bonios, Michael et al.
In: Journal of the American College of Cardiology, Vol. 54, No. 17, 20.10.2009, p. 1619-1626.

Research output: Contribution to journal › Article › peer-review

Terrovitis, J, Lautamäki, R, Bonios, M, Fox, J, Engles, JM, Yu, J, Leppo, MK, Pomper, MG, Wahl, RL, Seidel, J, Tsui, BM, Bengel, FM, Abraham, MR & Marbán, E 2009, 'Noninvasive Quantification and Optimization of Acute Cell Retention by In Vivo Positron Emission Tomography After Intramyocardial Cardiac-Derived Stem Cell Delivery', Journal of the American College of Cardiology, vol. 54, no. 17, pp. 1619-1626. https://doi.org/10.1016/j.jacc.2009.04.097

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

abstract = "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 [18F]-fluoro-deoxy-glucose (18FDG) 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 with 18FDG 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.",

keywords = "PET, adenosine, cardiac stem cells, fibrin glue",

author = "John Terrovitis and Riikka Lautam{\"a}ki and Michael Bonios and James Fox and Engles, {James M.} and Jianhua Yu and Leppo, {Michelle K.} and Pomper, {Martin G.} and Wahl, {Richard L.} and Jurgen Seidel and Tsui, {Benjamin M.} and Bengel, {Frank M.} and Abraham, {M. Roselle} and Eduardo Marb{\'a}n",

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T1 - Noninvasive Quantification and Optimization of Acute Cell Retention by In Vivo Positron Emission Tomography After Intramyocardial Cardiac-Derived Stem Cell Delivery

AU - Terrovitis, John

AU - Lautamäki, Riikka

AU - Bonios, Michael

AU - Fox, James

AU - Engles, James M.

AU - Yu, Jianhua

AU - Leppo, Michelle K.

AU - Pomper, Martin G.

AU - Wahl, Richard L.

AU - Seidel, Jurgen

AU - Tsui, Benjamin M.

AU - Bengel, Frank M.

AU - Abraham, M. Roselle

AU - Marbán, Eduardo

PY - 2009/10/20

Y1 - 2009/10/20

N2 - 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 [18F]-fluoro-deoxy-glucose (18FDG) 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 with 18FDG 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.

AB - 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 [18F]-fluoro-deoxy-glucose (18FDG) 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 with 18FDG 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.

KW - PET

KW - adenosine

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

Abstract

Keywords

ASJC Scopus subject areas

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