Effect of the stop-flow technique on cardiac retention of c-kit positive human cardiac stem cells after intracoronary infusion in a porcine model of chronic ischemic cardiomyopathy

Matthew C.L. Keith, Yukichi Tokita, Xian Liang Tang, Shahab Ghafghazi, Joseph B. Moore, Kyung U. Hong, Julius B. Elmore, Alok R. Amraotkar, Haixun Guo, Brian L. Ganzel, Kendra J. Grubb, Michael P. Flaherty, Bathri N. Vajravelu, Marcin Wysoczynski, Roberto Bolli

Research output: Contribution to journalArticlepeer-review

Abstract

It is commonly thought that the optimal method for intracoronary administration of cells is to stop coronary flow during cell infusion, in order to prolong cell/vascular wall contact, enhance adhesion, and promote extravasation of cells into the interstitial space. However, occlusion of a coronary artery with a balloon involves serious risks of vascular damage and/or dissection, particularly in non-stented segments such as those commonly found in patients with heart failure. It remains unknown whether the use of the stop-flow technique results in improved donor cell retention. Acute myocardial infarction was produced in 14 pigs. One to two months later, pigs received 10 million indium-111 oxyquinoline (oxine)-labeled c-kitpos human cardiac stem cells (hCSCs) via intracoronary infusion with (n = 7) or without (n = 7) balloon inflation. Pigs received cyclosporine to prevent acute graft rejection. Animals were euthanized 24 h later and hearts harvested for radioactivity measurements. With the stop-flow technique, the retention of hCSCs at 24 h was 5.41 ± 0.80 % of the injected dose (n = 7), compared with 4.87 ± 0.62 % without coronary occlusion (n = 7), (P = 0.60). When cells are delivered intracoronarily in a clinically relevant porcine model of chronic ischemic cardiomyopathy, the use of the stop-flow technique does not result in greater myocardial cell retention at 24 h compared with non-occlusive infusion. These results have practical implications for the design of cell therapy trials. Our observations suggest that the increased risk of complications secondary to coronary manipulation and occlusion is not warranted.

Original languageEnglish (US)
Article number46
Pages (from-to)1-9
Number of pages9
JournalBasic Research in Cardiology
Volume110
Issue number5
DOIs
StatePublished - Sep 1 2015

Keywords

  • CSCs
  • Cardiac stem cells
  • Coronary stop flow
  • Intracoronary
  • Retention
  • c-kit

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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