Radiolabeled cell distribution after intramyocardial, intracoronary, and interstitial retrograde coronary venous delivery: Implications for current clinical trials

Dongming Hou, Eyas Al Shaykh Youssef, Todd J. Brinton, Ping Zhang, Pamela Rogers, Erik T. Price, Alan C. Yeung, Brian H. Johnstone, Paul G. Yock, Keith L. March

Research output: Contribution to journalArticle

435 Citations (Scopus)

Abstract

Background - Several clinical studies are evaluating the therapeutic potential of delivery of various progenitor cells for treatment of injured hearts. However, the actual fate of delivered cells has not been thoroughly assessed for any cell type. We evaluated the short-term fate of peripheral blood mononuclear cells (PBMNCs) after intramyocardial (IM), intracoronary (IC), and interstitial retrograde coronary venous (IRV) delivery in an ischemic swine model. Methods and Results - Myocardial ischemia was created by 45 minutes of balloon occlusion of the left anterior descending coronary artery. Six days later, 107 111indium-oxine-labeled human PBMNCs were delivered by IC (n=5), IM (n=6), or IRV (n=5) injection. The distribution of injected cells was assessed by γ-emission counting of harvested organs. For each delivery method, a significant fraction of delivered cells exited the heart into the pulmonary circulation, with 26±3% (IM), 47±1% (IC), and 43±3% (IRV) of cells found localized in the lungs. Within the myocardium, significantly more cells were retained after IM injection (11±3%) compared with IC (2.6±0.3%) (P<0.05) delivery. IRV delivery efficiency (3.2±1%) trended lower than IM infusion for PBMNCs, but this difference did not reach significance. The IM technique displayed the greatest variability in delivery efficiency by comparison with the other techniques. Conclusions - The majority of delivered cells is not retained in the heart for each delivery modality. The clinical implications of these findings are potentially significant, because cells with proangiogenic or other therapeutic effects could conceivably have effects in other organs to which they are not primarily targeted but to which they are distributed. Also, we found that although IM injection was more efficient, it was less consistent in the delivery of PBMNCs compared with IC and IRV techniques.

Original languageEnglish
JournalCirculation
Volume112
Issue number9 SUPPL.
DOIs
StatePublished - Aug 30 2005

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Clinical Trials
Blood Cells
Injections
Oxyquinoline
Balloon Occlusion
Pulmonary Circulation
Therapeutic Uses
Myocardial Ischemia
Coronary Vessels
Myocardium
Swine
Stem Cells
Lung
Therapeutics

Keywords

  • Catheters
  • Cells
  • Ischemia
  • Myocardial infarction

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

Cite this

Radiolabeled cell distribution after intramyocardial, intracoronary, and interstitial retrograde coronary venous delivery : Implications for current clinical trials. / Hou, Dongming; Youssef, Eyas Al Shaykh; Brinton, Todd J.; Zhang, Ping; Rogers, Pamela; Price, Erik T.; Yeung, Alan C.; Johnstone, Brian H.; Yock, Paul G.; March, Keith L.

In: Circulation, Vol. 112, No. 9 SUPPL., 30.08.2005.

Research output: Contribution to journalArticle

Hou, D, Youssef, EAS, Brinton, TJ, Zhang, P, Rogers, P, Price, ET, Yeung, AC, Johnstone, BH, Yock, PG & March, KL 2005, 'Radiolabeled cell distribution after intramyocardial, intracoronary, and interstitial retrograde coronary venous delivery: Implications for current clinical trials', Circulation, vol. 112, no. 9 SUPPL.. https://doi.org/10.1161/CIRCULATIONAHA.104.526749
Hou, Dongming ; Youssef, Eyas Al Shaykh ; Brinton, Todd J. ; Zhang, Ping ; Rogers, Pamela ; Price, Erik T. ; Yeung, Alan C. ; Johnstone, Brian H. ; Yock, Paul G. ; March, Keith L. / Radiolabeled cell distribution after intramyocardial, intracoronary, and interstitial retrograde coronary venous delivery : Implications for current clinical trials. In: Circulation. 2005 ; Vol. 112, No. 9 SUPPL.
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abstract = "Background - Several clinical studies are evaluating the therapeutic potential of delivery of various progenitor cells for treatment of injured hearts. However, the actual fate of delivered cells has not been thoroughly assessed for any cell type. We evaluated the short-term fate of peripheral blood mononuclear cells (PBMNCs) after intramyocardial (IM), intracoronary (IC), and interstitial retrograde coronary venous (IRV) delivery in an ischemic swine model. Methods and Results - Myocardial ischemia was created by 45 minutes of balloon occlusion of the left anterior descending coronary artery. Six days later, 107 111indium-oxine-labeled human PBMNCs were delivered by IC (n=5), IM (n=6), or IRV (n=5) injection. The distribution of injected cells was assessed by γ-emission counting of harvested organs. For each delivery method, a significant fraction of delivered cells exited the heart into the pulmonary circulation, with 26±3{\%} (IM), 47±1{\%} (IC), and 43±3{\%} (IRV) of cells found localized in the lungs. Within the myocardium, significantly more cells were retained after IM injection (11±3{\%}) compared with IC (2.6±0.3{\%}) (P<0.05) delivery. IRV delivery efficiency (3.2±1{\%}) trended lower than IM infusion for PBMNCs, but this difference did not reach significance. The IM technique displayed the greatest variability in delivery efficiency by comparison with the other techniques. Conclusions - The majority of delivered cells is not retained in the heart for each delivery modality. The clinical implications of these findings are potentially significant, because cells with proangiogenic or other therapeutic effects could conceivably have effects in other organs to which they are not primarily targeted but to which they are distributed. Also, we found that although IM injection was more efficient, it was less consistent in the delivery of PBMNCs compared with IC and IRV techniques.",
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T1 - Radiolabeled cell distribution after intramyocardial, intracoronary, and interstitial retrograde coronary venous delivery

T2 - Implications for current clinical trials

AU - Hou, Dongming

AU - Youssef, Eyas Al Shaykh

AU - Brinton, Todd J.

AU - Zhang, Ping

AU - Rogers, Pamela

AU - Price, Erik T.

AU - Yeung, Alan C.

AU - Johnstone, Brian H.

AU - Yock, Paul G.

AU - March, Keith L.

PY - 2005/8/30

Y1 - 2005/8/30

N2 - Background - Several clinical studies are evaluating the therapeutic potential of delivery of various progenitor cells for treatment of injured hearts. However, the actual fate of delivered cells has not been thoroughly assessed for any cell type. We evaluated the short-term fate of peripheral blood mononuclear cells (PBMNCs) after intramyocardial (IM), intracoronary (IC), and interstitial retrograde coronary venous (IRV) delivery in an ischemic swine model. Methods and Results - Myocardial ischemia was created by 45 minutes of balloon occlusion of the left anterior descending coronary artery. Six days later, 107 111indium-oxine-labeled human PBMNCs were delivered by IC (n=5), IM (n=6), or IRV (n=5) injection. The distribution of injected cells was assessed by γ-emission counting of harvested organs. For each delivery method, a significant fraction of delivered cells exited the heart into the pulmonary circulation, with 26±3% (IM), 47±1% (IC), and 43±3% (IRV) of cells found localized in the lungs. Within the myocardium, significantly more cells were retained after IM injection (11±3%) compared with IC (2.6±0.3%) (P<0.05) delivery. IRV delivery efficiency (3.2±1%) trended lower than IM infusion for PBMNCs, but this difference did not reach significance. The IM technique displayed the greatest variability in delivery efficiency by comparison with the other techniques. Conclusions - The majority of delivered cells is not retained in the heart for each delivery modality. The clinical implications of these findings are potentially significant, because cells with proangiogenic or other therapeutic effects could conceivably have effects in other organs to which they are not primarily targeted but to which they are distributed. Also, we found that although IM injection was more efficient, it was less consistent in the delivery of PBMNCs compared with IC and IRV techniques.

AB - Background - Several clinical studies are evaluating the therapeutic potential of delivery of various progenitor cells for treatment of injured hearts. However, the actual fate of delivered cells has not been thoroughly assessed for any cell type. We evaluated the short-term fate of peripheral blood mononuclear cells (PBMNCs) after intramyocardial (IM), intracoronary (IC), and interstitial retrograde coronary venous (IRV) delivery in an ischemic swine model. Methods and Results - Myocardial ischemia was created by 45 minutes of balloon occlusion of the left anterior descending coronary artery. Six days later, 107 111indium-oxine-labeled human PBMNCs were delivered by IC (n=5), IM (n=6), or IRV (n=5) injection. The distribution of injected cells was assessed by γ-emission counting of harvested organs. For each delivery method, a significant fraction of delivered cells exited the heart into the pulmonary circulation, with 26±3% (IM), 47±1% (IC), and 43±3% (IRV) of cells found localized in the lungs. Within the myocardium, significantly more cells were retained after IM injection (11±3%) compared with IC (2.6±0.3%) (P<0.05) delivery. IRV delivery efficiency (3.2±1%) trended lower than IM infusion for PBMNCs, but this difference did not reach significance. The IM technique displayed the greatest variability in delivery efficiency by comparison with the other techniques. Conclusions - The majority of delivered cells is not retained in the heart for each delivery modality. The clinical implications of these findings are potentially significant, because cells with proangiogenic or other therapeutic effects could conceivably have effects in other organs to which they are not primarily targeted but to which they are distributed. Also, we found that although IM injection was more efficient, it was less consistent in the delivery of PBMNCs compared with IC and IRV techniques.

KW - Catheters

KW - Cells

KW - Ischemia

KW - Myocardial infarction

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