103[ 17 ]. EPDCs have been shown to contribute to coronary vascular smooth muscle
cells and fibroblasts but whether they also differentiate to cardiomyocytes remains
controversial. Recently, a population of EPDCs with mesenchymal-like properties,
termed as colony-forming units—fibroblasts has been characterized in the develop-
ing and adult mouse heart [ 18 ]. Their role in cardiac repair and homeostasis, how-
ever, still needs to be investigated (Table 7.1).
Given the multiple cell surface markers that have been associated with CSCs, it
is discernible that CSCs is a heterogenous group of cells that includes early uncom-
mitted cells and lineage-committed cells, quiescent and activated cells, cycling and
non-cycling cells.
7.3 CSCs and In Vivo Fate-Tracing Studies
The identification of multiple putative CSC populations raises the question of
whether any of them also participates in cellular homeostasis of the myocardium
throughout life and its repair in response to damage in vivo. Many studies have
investigated the contribution of endogenous CSCs towards cardiomyocyte renewal
in vivo through genetic fate-mapping studies, albeit with varying results. In these
studies, the expression of a fluorescent reporter gene is placed under the control of
promoters coding for myocyte and vascular proteins to track the origin and fate of
cells in experimental animals.
Table 7.1 Phenotype of different reported populations of cardiac stem cells
S. no. CSC population Source Phenotype References- c-kitpos CSCs Myocardium CD34neg, CD45neg, Sca-1pos,
Abcg2pos, CD105pos
[ 1 , 9 ]- Sca1pos CSCs Myocardium CD34neg, CD45neg, FLK1neg,
c-kitlow, GATA4pos, NKX2-
5low, MEF2Cpos
[ 10 , 11 ]- Side population cells Myocardium CD34pos, CD45pos, Abcg2pos,
Sca1pos, c-kitpos, NKX2-5neg,
GATA4neg
[ 12 ]- Isl-1pos cardiac
progenitor cells
Myocardium CD31neg, Sca1neg, ckitneg,
GATA4pos, NKX2.5pos[ 13 , 14 ]- Cardiosphere-
derived cells
Myocardium CD105pos, CD34pos,
CD45pos, Abcg2pos, Sca1pos,
c-kitlow[ 15 , 16 ]- Epicardium-derived
progenitor cells
Epicardium Wt1pos, NKX2.5pos, Isl1pos,
ckitneg, Sca1pos[ 17 ]- Colony-forming
units - fibroblasts
Epicardium Sca-1pos, PDGFRαpos,
CD31neg, c-kitlow, CD45neg,
FLK1neg, CD44pos, CD90pos,
CD29pos, and CD105pos[ 18 ]7 The Emerging Role of Cardiac Stem Cells in Cardiac Regeneration