Dual roles for bone marrow‐derived Sca‐1 cells in cardiac function

• Published in: The FASEB journal 2017-07, Vol.31 (7), p.2905-2915
• Main Authors: Tobin, Stephanie W., Li, Shu‐Hong, Li, Jiao, Wu, Jun, Yeganeh, Azadeh, Yu, Pan, Weisel, Richard D., Li, Ren‐Ke
• Format: Article
• Language: English
• Subjects: aging; Animals; Bone healing; Bone marrow; Bone Marrow Cells - physiology; cardiovascular disease; Cell Line; Cell surface; Fluorescence; Gene expression; Gene Expression Regulation - physiology; Green fluorescent protein; Green Fluorescent Proteins; Healing; Heart; Heart diseases; Heart Diseases - metabolism; IL-1β; Inflammation; Inflammation - metabolism; Inflammatory response; Macrophages; Mice; Myocardial infarction; Myocardium - metabolism; Population studies; Recruitment; Serum response factor; Stem cell antigen 1; Stem cell transplantation; Stem cells; Stem Cells - physiology; Surface markers; Transcription, Genetic - physiology; Up-Regulation; Vascular endothelial growth factor
• ISSN: 0892-6638; 1530-6860
• DOI: 10.1096/fj.201601363RR

ABSTRACT 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 Il‐1β. 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. FASEB J. 31, 2905–2915 (2017). www.fasebj.org