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Myocardial Infarction in Neonatal Mice, A Model of Cardiac Regeneration
Published on: May 24, 2016
Dynamics of human myocardial progenitor cell populations in the neonatal period
Gabriel Amir1, Xiaoyuan Ma, V Mohan Reddy
1Department of Cardiothoracic Surgery, Pediatric Division, Stanford University School of Medicine, Stanford, California 94305-5407, USA.
Insights
Neonatal heart muscle contains progenitor cells, but their numbers decrease in the first month after birth. This decline impacts potential regenerative therapies for congenital heart disease.
Area of Science:
- Cardiovascular Research
- Developmental Biology
- Regenerative Medicine
Background:
- Pluripotent cardiac progenitor cells in the myocardium hold promise for injury repair.
- Understanding these cells in pediatric congenital heart disease (CHD) is crucial for developing new therapeutic strategies.
Purpose of the Study:
- To identify and quantify progenitor cell populations in human neonatal myocardium.
- To assess the proliferative capacity of differentiated cardiac myocytes in early postnatal development.
Main Methods:
- Analyzed right ventricular biopsies from 32 CHD patients (2-93 days old).
- Used immunologic markers: SSEA-4, Isl1, c-kit, Nkx2.5, SERCA2 for cell lineage.
- Assessed proliferation using Ki67 marker.
Main Results:
- Neonatal myocardium harbors progenitor and transitional cells expressing both progenitor and myocyte markers.
- Cells coexpressing pluripotent (c-kit) and myocyte (SERCA2) markers were observed.
- A significant decline in the density of c-kit+ (p=0.0013) and Nkx2.5+ (p=0.0001) cells occurred within the first postnatal month.
- The percentage of Ki67+ cells decreased over the first three postnatal months (p=0.0030).
Conclusions:
- The infant heart contains incompletely differentiated cardiomyocyte cells.
- The density of cardiac progenitor cells diminishes during the first postnatal month, potentially limiting regenerative capacity.
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.
