title: 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.
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-kit(pos) 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.
authors.affiliation: Institute of Molecular Cardiology, University of Louisville, 550 S Jackson Street, ACB Bldg, 3rd Floor, Louisville, KY, 40202, USA.
authors.forename: Matthew C L
authors.initials: MC
authors.lastname: Keith
authors.forename: Yukichi
authors.initials: Y
authors.lastname: Tokita
authors.forename: Xian-Liang
authors.initials: XL
authors.lastname: Tang
authors.forename: Shahab
authors.initials: S
authors.lastname: Ghafghazi
authors.forename: Joseph B
authors.initials: JB
authors.lastname: Moore
authors.forename: Kyung U
authors.initials: KU
authors.lastname: Hong
authors.forename: Julius B
authors.initials: JB
authors.lastname: Elmore
authors.forename: Alok R
authors.initials: AR
authors.lastname: Amraotkar
authors.forename: Haixun
authors.initials: H
authors.lastname: Guo
authors.forename: Brian L
authors.initials: BL
authors.lastname: Ganzel
authors.forename: Kendra J
authors.initials: KJ
authors.lastname: Grubb
authors.forename: Michael P
authors.initials: MP
authors.lastname: Flaherty
authors.forename: Bathri N
authors.initials: BN
authors.lastname: Vajravelu
authors.forename: Marcin
authors.initials: M
authors.lastname: Wysoczynski
authors.forename: Roberto
authors.initials: R
authors.lastname: Bolli
mesh_terms: D000818:Animals; D002469:Cell Separation; D004195:Disease Models, Animal; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D017202:Myocardial Ischemia / Q000601:surgery*; D032383:Myocytes, Cardiac / Q000637:transplantation*; D019009:Proto-Oncogene Proteins c-kit; D033581:Stem Cell Transplantation / Q000379:methods*; D034421:Sus scrofa
chemical_list: D019009:Proto-Oncogene Proteins c-kit