Myocardial substrate and route of administration determine acute cardiac retention and lung biodistribution of cardiosphere-derived cells

Michael Bonios, John Terrovitis, Connie Y. Chang, James M. Engles, Takahiro Higuchi, Riikka Lautamäki, Jianhua Yu, James Fox, Martin Pomper, Richard L. Wahl, Benjamin M. Tsui, Brian O'Rourke, Frank M. Bengel, Eduardo Marbán, M. Roselle Abraham

Research output: Contribution to journalArticle

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Abstract

Background. Quantification of acute myocardial retention and lung bio-distribution of cardiosphere-derived cells (CDCs) following transplantation is important to improve engraftment. Methods and results. We studied acute(1 hour) cardiac/lung retention in 4 groups (n 5 25) of rats (normal-NL, acute ischemia-reperfusion-AI-RM, acute permanent ligation-PL, and chronic infarct by ischemia-reperfusion-CI-R) using intra-myocardial delivery, 1 group using intracoronary delivery (acute ischemia-reperfusion, AI-RC, n 5 5) and 1 group using intravenous delivery (acute ischemia-reperfusion, AI-RV, n 5 5) of CDCs by PET. Cardiac retention was similar in the NL, AI-RM, CI-R, and A-IRC groups (13.6% ± 2.3% vs 12.0% ± 3.9% vs 9.9 ± 2.8 vs 15.4% ± 5.5%; P 5 NS), but higher in PL animals (22.9% ± 5.2%; P < .05). Low cardiac retention was associated with significantly higher lung activity in NL and AI-RM groups (43.3% ± 5.6% and 39.9% ± 9.3%), compared to PL (28.5% ± 5.9%), CI-R (20.2% ± 9.3%), and A-IRC (19.9% ± 5.6%) animals (P < .05 vs AI-RM and NL). Lung activity was highest following intravenous CDC delivery (55.1% ± 9.3%, P < .001) and was associated with very low cardiac retention (0.8% ± 1.06%). Two-photon microscopy indicated that CDCs escaped to the lungs via the coronary veins following intra-myocardial injection. Conclusions. Acute cardiac retention and lung bio-distribution vary with the myocardial substrate and injection route. Intra-myocardially injected CDCs escape into the lungs via coronary veins, an effect that is more pronounced in perfused myocardium.

Original languageEnglish
Pages (from-to)443-450
Number of pages8
JournalJournal of Nuclear Cardiology
Volume18
Issue number3
DOIs
Publication statusPublished - May 1 2011
Externally publishedYes

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Lung
Reperfusion
Ischemia
Coronary Vessels
Injections
Cell Transplantation
Photons
Ligation
Microscopy
Myocardium

Keywords

  • Acute heart retention
  • Lung bio-distribution
  • PET
  • Stem cells

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging
  • Cardiology and Cardiovascular Medicine

Cite this

Myocardial substrate and route of administration determine acute cardiac retention and lung biodistribution of cardiosphere-derived cells. / Bonios, Michael; Terrovitis, John; Chang, Connie Y.; Engles, James M.; Higuchi, Takahiro; Lautamäki, Riikka; Yu, Jianhua; Fox, James; Pomper, Martin; Wahl, Richard L.; Tsui, Benjamin M.; O'Rourke, Brian; Bengel, Frank M.; Marbán, Eduardo; Abraham, M. Roselle.

In: Journal of Nuclear Cardiology, Vol. 18, No. 3, 01.05.2011, p. 443-450.

Research output: Contribution to journalArticle

Bonios, M, Terrovitis, J, Chang, CY, Engles, JM, Higuchi, T, Lautamäki, R, Yu, J, Fox, J, Pomper, M, Wahl, RL, Tsui, BM, O'Rourke, B, Bengel, FM, Marbán, E & Abraham, MR 2011, 'Myocardial substrate and route of administration determine acute cardiac retention and lung biodistribution of cardiosphere-derived cells', Journal of Nuclear Cardiology, vol. 18, no. 3, pp. 443-450. https://doi.org/10.1007/s12350-011-9369-9
Bonios, Michael ; Terrovitis, John ; Chang, Connie Y. ; Engles, James M. ; Higuchi, Takahiro ; Lautamäki, Riikka ; Yu, Jianhua ; Fox, James ; Pomper, Martin ; Wahl, Richard L. ; Tsui, Benjamin M. ; O'Rourke, Brian ; Bengel, Frank M. ; Marbán, Eduardo ; Abraham, M. Roselle. / Myocardial substrate and route of administration determine acute cardiac retention and lung biodistribution of cardiosphere-derived cells. In: Journal of Nuclear Cardiology. 2011 ; Vol. 18, No. 3. pp. 443-450.
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AU - Bonios, Michael

AU - Terrovitis, John

AU - Chang, Connie Y.

AU - Engles, James M.

AU - Higuchi, Takahiro

AU - Lautamäki, Riikka

AU - Yu, Jianhua

AU - Fox, James

AU - Pomper, Martin

AU - Wahl, Richard L.

AU - Tsui, Benjamin M.

AU - O'Rourke, Brian

AU - Bengel, Frank M.

AU - Marbán, Eduardo

AU - Abraham, M. Roselle

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N2 - Background. Quantification of acute myocardial retention and lung bio-distribution of cardiosphere-derived cells (CDCs) following transplantation is important to improve engraftment. Methods and results. We studied acute(1 hour) cardiac/lung retention in 4 groups (n 5 25) of rats (normal-NL, acute ischemia-reperfusion-AI-RM, acute permanent ligation-PL, and chronic infarct by ischemia-reperfusion-CI-R) using intra-myocardial delivery, 1 group using intracoronary delivery (acute ischemia-reperfusion, AI-RC, n 5 5) and 1 group using intravenous delivery (acute ischemia-reperfusion, AI-RV, n 5 5) of CDCs by PET. Cardiac retention was similar in the NL, AI-RM, CI-R, and A-IRC groups (13.6% ± 2.3% vs 12.0% ± 3.9% vs 9.9 ± 2.8 vs 15.4% ± 5.5%; P 5 NS), but higher in PL animals (22.9% ± 5.2%; P < .05). Low cardiac retention was associated with significantly higher lung activity in NL and AI-RM groups (43.3% ± 5.6% and 39.9% ± 9.3%), compared to PL (28.5% ± 5.9%), CI-R (20.2% ± 9.3%), and A-IRC (19.9% ± 5.6%) animals (P < .05 vs AI-RM and NL). Lung activity was highest following intravenous CDC delivery (55.1% ± 9.3%, P < .001) and was associated with very low cardiac retention (0.8% ± 1.06%). Two-photon microscopy indicated that CDCs escaped to the lungs via the coronary veins following intra-myocardial injection. Conclusions. Acute cardiac retention and lung bio-distribution vary with the myocardial substrate and injection route. Intra-myocardially injected CDCs escape into the lungs via coronary veins, an effect that is more pronounced in perfused myocardium.

AB - Background. Quantification of acute myocardial retention and lung bio-distribution of cardiosphere-derived cells (CDCs) following transplantation is important to improve engraftment. Methods and results. We studied acute(1 hour) cardiac/lung retention in 4 groups (n 5 25) of rats (normal-NL, acute ischemia-reperfusion-AI-RM, acute permanent ligation-PL, and chronic infarct by ischemia-reperfusion-CI-R) using intra-myocardial delivery, 1 group using intracoronary delivery (acute ischemia-reperfusion, AI-RC, n 5 5) and 1 group using intravenous delivery (acute ischemia-reperfusion, AI-RV, n 5 5) of CDCs by PET. Cardiac retention was similar in the NL, AI-RM, CI-R, and A-IRC groups (13.6% ± 2.3% vs 12.0% ± 3.9% vs 9.9 ± 2.8 vs 15.4% ± 5.5%; P 5 NS), but higher in PL animals (22.9% ± 5.2%; P < .05). Low cardiac retention was associated with significantly higher lung activity in NL and AI-RM groups (43.3% ± 5.6% and 39.9% ± 9.3%), compared to PL (28.5% ± 5.9%), CI-R (20.2% ± 9.3%), and A-IRC (19.9% ± 5.6%) animals (P < .05 vs AI-RM and NL). Lung activity was highest following intravenous CDC delivery (55.1% ± 9.3%, P < .001) and was associated with very low cardiac retention (0.8% ± 1.06%). Two-photon microscopy indicated that CDCs escaped to the lungs via the coronary veins following intra-myocardial injection. Conclusions. Acute cardiac retention and lung bio-distribution vary with the myocardial substrate and injection route. Intra-myocardially injected CDCs escape into the lungs via coronary veins, an effect that is more pronounced in perfused myocardium.

KW - Acute heart retention

KW - Lung bio-distribution

KW - PET

KW - Stem cells

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