Systemic Delivery of Bone Marrow–Derived Mesenchymal Stem Cells to the Infarcted Myocardium

Author:

Barbash Israel M.1,Chouraqui Pierre1,Baron Jack1,Feinberg Micha S.1,Etzion Sharon1,Tessone Ariel1,Miller Liron1,Guetta Esther1,Zipori Dov1,Kedes Laurence H.1,Kloner Robert A.1,Leor Jonathan1

Affiliation:

1. 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...

Abstract

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 99m Tc exametazime, fluorescent dye, LacZ marker gene, or bromodeoxyuridine. Rats were subjected to MI by transient coronary artery occlusion or to sham MI. 99m Tc-labeled cells (4×10 6 ) 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 99m Tc-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.

Publisher

Ovid Technologies (Wolters Kluwer Health)

Subject

Physiology (medical),Cardiology and Cardiovascular Medicine

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3