Circulation. 2003;108:863-868
Published online before print August 4, 2003, doi: 10.1161/01.CIR.0000084828.50310.6A
Published online before print August 4, 2003, doi: 10.1161/01.CIR.0000084828.50310.6A
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(Circulation. 2003;108:863.)
© 2003 American Heart Association, Inc.
Basic Science Reports |
Systemic Delivery of Bone Marrow–Derived Mesenchymal Stem Cells to the Infarcted Myocardium
Feasibility, Cell Migration, and Body Distribution
From the Neufeld Cardiac Research Institute (I.M.B., P.C., J.B., M.S.F., S.E., A.T., L.M., J.L.) and Danek Gertner Institute of Human Genetics (E.G.), Sheba Medical Center, Tel-Hashomer, Israel; Department of Molecular Cell Biology (D.Z.), Weizmann Institute of Science, Rehovot, Israel; Institute for Genetic Medicine (L.H.K., R.A.K.), Department of Biochemistry & Molecular Biology, Los Angeles, Calif; Department of Medicine (L.H.K.), Keck School of Medicine of the University of Southern California, Los Angeles, Calif; and Heart Institute (R.A.K.), Good Samaritan Hospital, Los Angeles, Calif.
Correspondence to Jonathan Leor, MD, FACC, FESC, Neufeld Cardiac Research Institute, Sheba Medical Center, Tel-Hashomer 52621, Israel. E-mail leorj{at}post.tau.ac.il
Received February 11, 2002; de novo received February 10, 2003; revision received April 17, 2003; accepted April 25, 2003.
Background— Systemic delivery of bone marrow–derived mesenchymal stem cells (BM-MSCs) is an attractive approach for myocardial repair. We aimed to test this strategy in a rat model after myocardial infarction (MI).
Methods and Results— BM-MSCs were obtained from rat bone marrow, expanded in vitro to a purity of >50%, and labeled with 99mTc exametazime, fluorescent dye, LacZ marker gene, or bromodeoxyuridine. Rats were subjected to MI by transient coronary artery occlusion or to sham MI. 99mTc-labeled cells (4x106) were transfused into the left ventricular cavity of MI rats either at 2 or 10 to 14 days after MI and were compared with sham-MI rats or MI rats treated with intravenous infusion. Gamma camera imaging and isolated organ counting 4 hours after intravenous infusion revealed uptake of the 99mTc-labeled cells mainly in the lungs, with significantly smaller amounts in the liver, heart, and spleen. Delivery by left ventricular cavity infusion resulted in drastically lower lung uptake, better uptake in the heart, and specifically higher uptake in infarcted compared with sham-MI hearts. Histological examination at 1 week after infusion identified labeled cells either in the infarcted or border zone but not in remote viable myocardium or sham-MI hearts. Labeled cells were also identified in the lung, liver, spleen, and bone marrow.
Conclusions— Systemic intravenous delivery of BM-MSCs to rats after MI, although feasible, is limited by entrapment of the donor cells in the lungs. Direct left ventricular cavity infusion enhances migration and colonization of the cells preferentially to the ischemic myocardium.
Key Words: cells • myocardial infarction • nuclear medicine • transplantation
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