Dynamics of human myocardial progenitor cell populations in the neonatal period.
BACKGROUND
Pluripotent cardiac progenitor cells resident in myocardium offer a potentially promising role in promoting recovery from injury. In pediatric congenital heart disease (CHD) patients, manipulation of resident progenitor cells may provide important new approaches to improving outcomes. Our study goals were to identify and quantitate populations of progenitor cells in human neonatal myocardium during the early postnatal period and determine the proliferative capacity of differentiated cardiac myocytes.


METHODS
Immunologic markers of cell lineage (stage-specific embryonic antigen 4 [SSEA-4], islet cell antigen 1 [Isl1], c-kit, Nkx2.5, sarcoplasmic reticulum calcium-regulated ATPase type 2 [SERCA2]) and proliferation (Ki67) were localized in right ventricular biopsies from 32 CHD patients aged 2 to 93 days.


RESULTS
Neonatal myocardium contains progenitor cells and transitional cells expressing progenitor and differentiated myocyte marker proteins. Some cells expressed the pluripotent cell marker c-kit and also coexpressed the myocyte marker SERCA2. Multipotent progenitor cells, identified by the expression of Isl1, were found. Ki67 was expressed in some myocytes and in nonmyocyte cells. A few cells expressing SSEA-4 and Isl1 were observed during the early postnatal period. Cells expressing c-kit, the premyocyte marker Nkx2.5, and Ki67 were found throughout the first postnatal month. A progressive decline in cell density during the first postnatal month was observed for c-kit+ cells (p = 0.0013) and Nkx2.5+ cells (p = 0.0001). The percentage of cells expressing Ki67 declined during the first 3 postnatal months (p = 0.0030).


CONCLUSIONS
Cells in an incomplete state of cardiomyocyte differentiation continue to reside in the infant heart. However, the relative density of progenitor cells declines during the first postnatal month.
Amir
Gabriel
G
Department of Cardiothoracic Surgery, Pediatric Division, Stanford University School of Medicine, Stanford, California 94305-5407, USA.
Ma
Xiaoyuan
X
Reddy
V Mohan
VM
Hanley
Frank L
FL
Reinhartz
Olaf
O
Ramamoorthy
Chandra
C
Riemer
R Kirk
RK
D000704:Analysis of Variance; D006348:Cardiac Surgical Procedures; D049109:Cell Proliferation; D002478:Cells, Cultured; D005260:Female; D006330:Heart Defects, Congenital / Q000175:diagnosis / Q000601:surgery; D006801:Humans; D007150:Immunohistochemistry; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D032383:Myocytes, Cardiac / Q000473:pathology / Q000502:physiology*; D011336:Probability; D019009:Proto-Oncogene Proteins c-kit / Q000378:metabolism / Q000502:physiology*; D012038:Regeneration / Q000502:physiology*; D012680:Sensitivity and Specificity; D013234:Stem Cells / Q000473:pathology / Q000502:physiology*
D019009:Proto-Oncogene Proteins c-kit