Postnatal Changes In Human Cardiac Myocyte Putative Precursor Cell Populations.
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Objective: The presence of pluripotent myocardial precursor cells (MPC) in myocardium has received much attention from the perspective of their potential role in assisting with post-infarct recovery in adults. The physiologic role of putative cardiac progenitor cells in the regeneration of damaged myocardium is presently uncertain. Our focus is the broader potential role of MPC in healing following cardiac surgery, especially in pediatric patients with congenital heart diseases (CHD). This study was initiated to evaluate changes in the proliferative capacity of cardiac cells in the immediate postnatal period, when many children with CHD undergo surgery and are critically dependent on rapid functional recovery of myocardium to escape morbidity.
Methods: Immunologic markers of proliferation as well as cell lineage were assessed to characterize cardiac cell populations in right ventricular biopsies obtained from congenital cardiac surgery patients in the 1st month of life (17 patients; age 2 to 30 days).
Results: Expression of the proliferation marker Ki67 was highly variable but exhibited a trend toward a decline over the 1st month (p>0.05; ANOVA). Cells expressing the homeobox gene and putative MPC marker Isl1 were few in number, unevenly distributed, observed only in during the 1st week of life and, where found, co-localized with Nkx2-5 expression. In contrast, cells expressing the receptor for Stem Cell Factor and putative MPC marker, c-kit were more evenly distributed, found throughout the 1st month of life, and co-localized with the expression of the early cardiac marker, Mef2. Two populations showed a distinct progressive decline during the fist month of life: c-kit+ cell density fell 24-fold and Nkx2-5+ cells by 5-fold (both changes p<0.01; ANOVA).
Conclusions: These studies demonstrate that cells in an incomplete state of cardiomyocyte differentiation continue to reside in the heart after birth, but their relative density declines steeply over the 1st month of life. Expansion of incompletely differentiated precursor cell populations may normally facilitate recovery from surgery or injury. Therapies that promote the expansion of precursor cell populations may prove to be a useful means to accelerate recovery from cardiac surgery. Their potential contribution may be even greater in the early newborn period, before these putative precursor populations decline.
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