Circulation Research. 2005
Published online before print June 9, 2005, doi: 10.1161/01.RES.0000173297.53793.fa
Published online before print June 9, 2005, doi: 10.1161/01.RES.0000173297.53793.fa
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Submitted on April 13, 2005
Revised on May 24, 2005
Accepted on May 31, 2005
CD31- but Not CD31+ Cardiac Side Population Cells Exhibit Functional Cardiomyogenic Differentiation
Otmar Pfister ;
From the Whitaker Cardiovascular Institute, Boston University School of Medicine, Mass.
* To whom correspondence should be addressed. E-mail: rliao{at}bu.edu.
Heart failure remains a leading cause of morbidity and mortality. The cellular mechanism underlying the development of cardiac dysfunction is a decrease in the number of viable cardiomyocytes. Recent observations have suggested that the adult heart may contain a progenitor cell population. Side population (SP) cells, characterized by a distinct Hoechst dye efflux pattern, have been shown to exist in multiple tissues and are capable of tissue-specific differentiation. In this report, we confirm the existence of a cardiac SP cell population, immunophenotypically distinct from bone marrow SP cells. Moreover, we demonstrate that among cardiac SP cells, the greatest potential for cardiomyogenic differentiation is restricted to cells negative for CD31 expression and positive for stem cell antigen 1 (Sca1) expression (CD31-/Sca1+). Furthermore, we determine that CD31-/Sca1+ cardiac SP cells are capable of both biochemical and functional cardiomyogenic differentiation into mature cardiomyocytes, with expression of cardiomyocyte-specific transcription factors and contractile proteins, as well as stimulated cellular contraction and intracellular calcium transients indistinguishable from adult cardiomyocytes. We also determine the necessity of cell-extrinsic signaling through coupling, although not fusion, with adult cardiomyocytes in regulating cardiomyogenic differentiation of cardiac SP cells. We, therefore, conclude that CD31-/Sca1+ cardiac SP cells represent a distinct cardiac progenitor cell population, capable of cardiomyogenic differentiation into mature cardiomyocytes through a process mediated by cellular coupling with adult cardiomyocytes.
Key words: cardiac side population cells • bone marrow side population cells • cardiomyogenic differentiation • cardiomyogenesis • CD31 • stem cell antigen 1
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