114
increased left ventricular thickness, and improve electrical stability following in situ
regeneration of cardiac, smooth muscle, and endothelial tissue throughout the
4-week follow-up period [ 83 ].
7.9 Conclusion
Given their lineage commitment to cardiac cell phenotype, undoubtedly, CSCs con-
stitute a powerful form of therapy for cardiac repair. However, there is definitely
something in the niche of heart that hinders the differentiation of cardiac precursors
into new functional cardiomyocytes. Thus, an identification of these factors is requi-
site to stimulate both endogenous cardiac repair and in vitro expansion of CSCs that
can be subsequently used for transplantation studies. Long-term objectives of CSC
therapy include optimization of dosages and route of administration, improved sur-
vival cell survival and engraftment with electromechanical integration into the heart,
hampering of adverse myocardial remodeling and significant improvement in con-
tractility of the diseased heart. Moreover, it is also worthwhile to further investigate
the role and underlying mechanisms of endogenous c-kit+ CSC-mediated in physio-
logical cardiac repair. An amalgamation of basic and clinical studies would be criti-
cal to reap the fruits from CSC-mediated therapy on clinical platforms. The targets
are challenging and strenuous but not impossible and absolutely worthwhile.
References
- Beltrami AP, Barlucchi L, Torella D, Baker M, Limana F, Chimenti S, et al. Adult cardiac stem
cells are multipotent and support myocardial regeneration. Cell. 2003;114:763–76. - Hosoda T, D'Amario D, Cabral-Da-Silva MC, Zheng H, Padin-Iruegas ME, Ogorek B, et al.
Clonality of mouse and human cardiomyogenesis in vivo. Proc Natl Acad Sci U S A.
2009;106:17169–74. - Linke A, Müller P, Nurzynska D, Casarsa C, Torella D, Nascimbene A, et al. Stem cells in the
dog heart are self-renewing, clonogenic, and multipotent and regenerate infarcted myocar-
dium, improving cardiac function. Proc Natl Acad Sci U S A. 2005;102:8966–71. - Naqvi N, Li M, Calvert JW, Tejada T, Lambert JP, Wu J, Kesteven SH, Holman SR, et al. A
proliferative burst during preadolescence establishes the final cardiomyocyte number. Cell.
2014;157:795–807. - Leri A, Rota M, Hosoda T, Goichberg P, Anversa P. Cardiac stem cell niches. Stem Cell Res.
2014;631-646. - Ferreira-Martins J, Ogórek B, Cappetta D, Matsuda A, Signore S, D'Amario, et al.
Cardiomyogenesis in the developing heart is regulated by c-kit-positive cardiac stem cells.
Circ Res. 2012;110:701–15. - Fazel S, Cimini M, Chen L, Li S, Angoulvant D, Fedak P, et al. Cardioprotective c-kit+ cells are
from the bone marrow and regulate the myocardial balance of angiogenic cytokines. J Clin
Invest. 2006;116:1865–77. - Chan SS-K, Shueh Y-Z, Liu Y-W, Hsieh PCH. Harnessing endogenous intra- and extra-cardiac
stem cells for cardiac regeneration—hope or hype? Drug Discov Today Ther Strateg.
2009;6:127–33.
S. Kaur et al.