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Myocardial substrate and route of administration determine acute cardiac retention and lung bio-distribution 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
Original Article

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 = 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) and 1 group using intravenous delivery (acute ischemia-reperfusion, AI-RV, n = 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 = 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.

Keywords

Stem cells acute heart retention PET lung bio-distribution 

Notes

Acknowledgments

We are grateful to Dana Kemmer for administrative assistance, Michelle Leppo, BS and Junaid M. Afzal, MBBS, MS for help with experiments.

Disclosures

Dr. Eduardo Marbán is founder and equity holder of Capricor, Inc. that works on CDCs. Capricor provided no funding for the present study. The remaining authors report no conflicts.

Supplementary material

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Supplementary material 1 (DOC 87 kb)
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Copyright information

© American Society of Nuclear Cardiology 2011

Authors and Affiliations

  • Michael Bonios
    • 1
  • John Terrovitis
    • 1
  • Connie Y. Chang
    • 1
  • James M. Engles
    • 1
  • Takahiro Higuchi
    • 1
  • Riikka Lautamäki
    • 1
  • Jianhua Yu
    • 1
  • James Fox
    • 1
  • Martin Pomper
    • 1
  • Richard L. Wahl
    • 1
  • Benjamin M. Tsui
    • 1
  • Brian O’Rourke
    • 1
  • Frank M. Bengel
    • 1
  • Eduardo Marbán
    • 2
  • M. Roselle Abraham
    • 1
  1. 1.Johns Hopkins UniversityBaltimoreUSA
  2. 2.Cedars-Sinai Heart InstituteLos AngelesUSA

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