 Tissue-Specific Stem CellsIFATS Collection: Human Adipose Tissue-Derived Stem Cells Induce Angiogenesis and Nerve Sprouting Following Myocardial Infarction, in Conjunction with Potent Preservation of Cardiac Function   § | | Liying Cai 1 2, Brian H. Johnstone 1 3, Todd G. Cook 1 3, Jian Tan 3, Michael C. Fishbein 4, Peng-Sheng Chen 3, Keith L. March 1 2 3 5 *¶ | 1Indiana Center for Vascular Biology and Medicine, Indiana University School of Medicine, Indianapolis, Indiana, USA
2Department of Cellular and Integrative Physiology, Indiana University School of Medicine, Indianapolis, Indiana, USA
3Krannert Institute of Cardiology, Indiana University School of Medicine, Indianapolis, Indiana, USA
4Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, USA
5R.L. Roudebush VA Medical Center, Indianapolis, Indiana, USA
| | email: Keith L. March (kmarch@iupui.edu) |
*Correspondence to Keith L. March, Indiana Center for Vascular Biology and Medicine, 975 West Walnut Street IB442, Indianapolis, Indiana, 46202, USA Author contributions: L.C.: conception and design, collection and assembly of data, data analysis and interpretation, manuscript drafting; B.H.J.: conception and design, data analysis and interpretation, manuscript revision; T.G.C., J.T., and M.C.F.: collection and assembly of data; P.-S.C.: data analysis and interpretation, manuscript revision; K.L.M.: manuscript revision, data analysis and interpretation, financial support, final approval of manuscript. Disclosure of potential conflicts of interest is found at the end of this article. §First published online in S TEM C ELLS Express September 4, 2008. ¶Telephone: 317-278-0130; Fax: 317-278-0089 Funded by:
 NIH; Grant Number: R01-HL77688-01
Veterans Administration Merit Review grant | Adipose tissue-derived stem cell • Myocardial infarction • Heart function • Angiogenesis |
| The administration of therapeutic cell types, such as stem and progenitor cells, has gained much interest for the limitation or repair of tissue damage caused by a variety of insults. However, it is still uncertain whether the morphological and functional benefits are mediated predominantly via cell differentiation or paracrine mechanisms. Here, we assessed the extent and mechanisms of adipose-derived stromal/stem cells (ASC)-dependent tissue repair in the context of acute myocardial infarction. Human ASCs in saline or saline alone was injected into the peri-infarct region in athymic rats following left anterior descending (LAD) coronary artery ligation. Cardiac function and structure were evaluated by serial echocardiography and histology. ASC-treated rats consistently exhibited better cardiac function, by all measures, than control rats 1 month following LAD occlusion. Left ventricular (LV) ejection fraction and fractional shortening were improved in the ASC group, whereas LV remodeling and dilation were limited in the ASC group compared with the saline control group. Anterior wall thinning was also attenuated by ASC treatment, and post-mortem histological analysis demonstrated reduced fibrosis in ASC-treated hearts, as well as increased peri-infarct density of both arterioles and nerve sprouts. Human ASCs were persistent at 1 month in the peri-infarct region, but they were not observed to exhibit significant cardiomyocyte differentiation. Human ASCs preserve heart function and augment local angiogenesis and cardiac nerve sprouting following myocardial infarction predominantly by the provision of beneficial trophic factors. STEM CELLS 2009;27:230-237 |
Received: 19 March 2008; Accepted: 22 August 2008 10.1634/stemcells.2008-0273 About DOI
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