TY - JOUR
T1 - Nestin expression in end-stage disease in dystrophin-deficient heart
T2 - Implications for regeneration from endogenous cardiac stem cells
AU - Berry, Suzanne E.
AU - Andruszkiewicz, Peter
AU - Chun, Ju Lan
AU - Hong, Jun
PY - 2013
Y1 - 2013
N2 - Nestin+ cardiac stem cells differentiate into striated cells following myocardial infarct. Transplantation of exogenous stem cells into myocardium of a murine model for Duchenne muscular dystrophy (DMD) increased proliferation of endogenous nestin+ stem cells and resulted in the appearance of nestin+ striated cells. This correlated with, and may be responsible for, prevention of dilated cardiomyopathy. We examined nestin+ stem cells in the myocardium of dystrophin/utrophin-deficient (mdx/utrn-/-) mice, a model for DMD. We found that 92% of nestin+ interstitial cells expressed Flk-1, a marker present on cardiac progenitor cells that differentiate into the cardiac lineage, and that a subset expressed Sca-1, present on adult cardiac cells that become cardiomyocytes. Nestin+ interstitial cells maintained expression of Flk-1 but lost Sca-1 expression with age and were present in lower numbers in dystrophin-deficient heart than in wild-type heart. Unexpectedly, large clusters of nestin+ striated cells ranging in size from 20 to 250 cells and extending up to 500 μm were present in mdx/utrn-/- heart near the end stage of disease. These cells were also present in dystrophindeficient mdx/utrn +/- and mdx heart but not wild-type heart. Nestin+ striated cells expressed cardiac troponin I, desmin, and Connexin 43 and correlated with proinflammatory CD68+ macrophages. Elongated nestin+ interstitial cells with striations were observed that did not express Flk-1 or the late cardiac marker cardiac troponin I but strongly expressed the early cardiac marker desmin. Nestin was also detected in endothelial and smooth muscle cells. These data indicate that new cardiomyocytes form in dystrophic heart, and nestin+ interstitial cells may generate them in addition to other cells of the cardiac lineage.
AB - Nestin+ cardiac stem cells differentiate into striated cells following myocardial infarct. Transplantation of exogenous stem cells into myocardium of a murine model for Duchenne muscular dystrophy (DMD) increased proliferation of endogenous nestin+ stem cells and resulted in the appearance of nestin+ striated cells. This correlated with, and may be responsible for, prevention of dilated cardiomyopathy. We examined nestin+ stem cells in the myocardium of dystrophin/utrophin-deficient (mdx/utrn-/-) mice, a model for DMD. We found that 92% of nestin+ interstitial cells expressed Flk-1, a marker present on cardiac progenitor cells that differentiate into the cardiac lineage, and that a subset expressed Sca-1, present on adult cardiac cells that become cardiomyocytes. Nestin+ interstitial cells maintained expression of Flk-1 but lost Sca-1 expression with age and were present in lower numbers in dystrophin-deficient heart than in wild-type heart. Unexpectedly, large clusters of nestin+ striated cells ranging in size from 20 to 250 cells and extending up to 500 μm were present in mdx/utrn-/- heart near the end stage of disease. These cells were also present in dystrophindeficient mdx/utrn +/- and mdx heart but not wild-type heart. Nestin+ striated cells expressed cardiac troponin I, desmin, and Connexin 43 and correlated with proinflammatory CD68+ macrophages. Elongated nestin+ interstitial cells with striations were observed that did not express Flk-1 or the late cardiac marker cardiac troponin I but strongly expressed the early cardiac marker desmin. Nestin was also detected in endothelial and smooth muscle cells. These data indicate that new cardiomyocytes form in dystrophic heart, and nestin+ interstitial cells may generate them in addition to other cells of the cardiac lineage.
KW - Cardiac
KW - Muscle stem cells
KW - Muscular dystrophy
KW - Nestin
KW - Sca-1
KW - Tissue regeneration
UR - http://www.scopus.com/inward/record.url?scp=84886549295&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84886549295&partnerID=8YFLogxK
U2 - 10.5966/sctm.2012-0174
DO - 10.5966/sctm.2012-0174
M3 - Article
C2 - 24068741
AN - SCOPUS:84886549295
SN - 2157-6564
VL - 2
SP - 848
EP - 861
JO - Stem Cells Translational Medicine
JF - Stem Cells Translational Medicine
IS - 11
ER -