Isolation, Characterization, and Spatial Distribution of Cardiac Progenitor Cells in the Sheep Heart
|Xuwei Hou1, Nancy Appleby1, Tania Fuentes1, Lawrence D. Longo2, Leonard L. Bailey3, Nahidh Hasaniya3 and Mary Kearns-Jonker1*|
|1Department of Pathology and Human Anatomy, Loma Linda University School of Medicine, Loma Linda, CA, USA|
|2Center for Perinatal Biology, Loma Linda University School of Medicine, Loma Linda, CA, USA|
|3Department of Cardiothoracic Surgery, Loma Linda University School of Medicine, Loma Linda, CA, USA|
|Corresponding Author :||Mary Kearns-Jonker
Department of Pathology and Human Anatomy
Loma Linda University School of Medicine
Loma Linda, CA, USA
E-mail: [email protected]
|Received August 29, 2012; Accepted October 08, 2012; Published October 11, 2012|
|Citation: Hou X, Appleby N, Fuentes T, Longo LD, Bailey LL, et al. (2012) Isolation, Characterization, and Spatial Distribution of Cardiac Progenitor Cells in the Sheep Heart. J Clin Exp Cardiolog S6:004. doi: 10.4172/2155-9880.S6-004|
|Copyright: © 2012 Hou X, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.|
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Background: Laboratory large animal models are important for establishing the efficacy of stem cell therapies that may be translated into clinical use. The similarity of ovine and human cardiovascular systems provides an opportunity to use the sheep as a large animal model in which to optimize cell-based treatments for the heart. Recent clinical trials in humans using endogenous cardiovascular progenitor cells report significant improvement in cardiac function following stem cell-based therapy. To date, however, endogenous cardiovascular progenitor cells have not been isolated from the sheep heart.
Methods: Cardiovascular cells expressing SSEA-4, CD105 and c-kit were isolated by flow cytometry and cloned from the right atrium of neonatal sheep. The expression of GATA-4, c-kit, and Isl1 was identified by PCR in the cloned cells. Immunohistochemical staining was used to compare the number of SSEA-4 positive cells in the right auricle, right atrium, left ventricle and the apex of the heart of fetal, neonatal and adult sheep. The number of SSEA4+cells was also compared in fetal, pregnant and non-pregnant adult sheep.
Results: Four distinct cardiac progenitor cell sub-populations were identified in sheep, including CD105+SSEA- 4+c-kit+Isl1+GATA-4+cells, CD105+SSEA-4+c-kit+Isl1+GATA-4-cells, CD105+SSEA-4-c-kit- Isl1+GATA-4-cells, and CD105+SSEA-4-c-kit+Isl1+GATA-4-cells. Immunohistochemical staining for SSEA-4 showed that labeled cells were most abundant in the right atrium of fetal hearts where niches of progenitor cells could be identified.
Conclusion: We determined the phenotype and distribution of cardiac progenitor cells in the sheep heart. The availability of cloned endogenous cardiac progenitor cells from sheep will provide a valuable resource for optimizing the conditions for cardiac repair in the ovine model.