期刊
FASEB JOURNAL
卷 31, 期 7, 页码 2905-2915出版社
FEDERATION AMER SOC EXP BIOL
DOI: 10.1096/fj.201601363RR
关键词
aging; cardiovascular disease; stem cells
资金
- Canadian Institutes of Health Research [332652]
- Bureau of Education of Guangzhou Municipality [1201581618]
Recruitment of stem cells from the bone marrow (BM) is an important aspect of cardiac healing that becomes inefficient with age. We investigated the role of young stem cell antigen 1 (Sca-1)-positive BM cells on the aged heart by microarray analysis after BM reconstitution. Sca-1(+) and Sca-1- BM cells from young green fluorescent protein (GFP)-positive mice were used to reconstitute the BM of aged mice. Myocardial infarction (MI) was induced 3 mo later. GFP(+) cells were more abundant in the BM, blood, and heart of Sca-1(+) mice, which corresponded to preserved cardiac function after MI. At baseline, Sca-1(+) BM reconstitution increased cardiac expression of serum response factor, vascular endothelial growth factor A, and myogenic genes, but reduced the expression of 1-1-113. After MI, inflammation was identified as a key difference between Sca-1(+) and Sca-1(+) groups, as cytokine expression and cell surface markers associated with inflammatory cells were up-regulated with Sca-1(+) reconstitution. Mac-3 and F4/80 staining showed that the postinfarction heart was composed of a mixture of GFP(+) (donor) macrophages, GFP(host) macrophages, and GFP(+) cells that did not contribute to the macrophage population. This study demonstrates that Sca-1(+) BM cells regulate cardiac healing though an acute inflammatory response and also before injury by stimulating formation of a beneficial cardiac niche. Tobin, S. W., Li, S.-H., Li, J., Wu, J., Yeganeh, A., Yu, P., Weisel, R. D., Li, R.-K. Dual roles for bone marrow-derived Sca-1 cells in cardiac function.
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