Evolution of The c-kit Positive Cell Response to Pathological Challenge in the Myocardium

¹ San Diego State University, SDSU Heart Institute, Department of Biology, NLS 426, 5500 Campanile Drive, San Diego, CA 92182
² Università Milano-Bicocca-Piazza delle Scienze, Milan, Italy
³ Invitrogen Corporation, Hopkinton MA 01748

^* To whom correspondence should be addressed. E-mail: sussman{at}heart.sdsu.edu.

	Abstract

Cumulative evidence indicates that myocardium responds to growth or injury by recruitment of stem and/or progenitor cells that participate in repair and regenerative processes. Unequivocal identification of this population has been hampered by lack of reagents or markers specific to the recruited population, leading to controversies regarding the nature of these cells. Utilization of a transgenic mouse expressing green fluorescent protein driven by the c-kit promoter allows for unambiguous identification of this cell population. GFP driven by the c-kit promoter labels a fraction of the c-kit+ cells recognized by antibody labeling for c-kit protein. Expression of GFP by the c-kit promoter and accumulation of GFP-positive cells in the myocardium is relatively high at birth compared to adult and declines between postnatal weeks one and two, which tracks in parallel with expression of c-kit protein and c-kit positive cells. Acute cardiomyopathic injury by infarction prompts increased expression of both GFP protein and GFP-labeled cells in the region of infarction relative to remote myocardium. Similar increases are observed for c-kit protein and cells with a slightly earlier onset and decline relative to the GFP signal. Cells co-expressing GFP, c-kit, and cardiogenic markers were apparent at 1-2 weeks post-infarction. Cardiac resident c-kit+ cell cultures derived from the transgenic line express GFP that is diminished in parallel with c-kit by induction of differentiation. The use of genetically engineered mice validates and extends the concept of c-kit+ cells participating in the response to myocardial injury.

This article has been cited by other articles:

				J. A. Muraski, K. M. Fischer, W. Wu, C. T. Cottage, P. Quijada, M. Mason, S. Din, N. Gude, R. Alvarez Jr, M. Rota, et al. Pim-1 kinase antagonizes aspects of myocardial hypertrophy and compensation to pathological pressure overload PNAS, September 16, 2008; 105(37): 13889 - 13894. [Abstract] [Full Text] [PDF]

				S. Siddiqi, N. Gude, T. Hosoda, J. Muraski, M. Rubio, G. Emmanuel, J. Fransioli, S. Vitale, C. Parolin, D. D'Amario, et al. Myocardial Induction of Nucleostemin in Response to Postnatal Growth and Pathological Challenge Circ. Res., July 3, 2008; 103(1): 89 - 97. [Abstract] [Full Text] [PDF]