Nestin expression in end-stage disease in dystrophin-deficient heart: Implications for regeneration from endogenous cardiac stem cells

Suzanne E. Berry, Peter Andruszkiewicz, Ju Lan Chun, Jun Hong

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish (US)
Pages (from-to)848-861
Number of pages14
JournalStem Cells Translational Medicine
Volume2
Issue number11
DOIs
StatePublished - 2013
Externally publishedYes

Keywords

  • Cardiac
  • Muscle stem cells
  • Muscular dystrophy
  • Nestin
  • Sca-1
  • Tissue regeneration

ASJC Scopus subject areas

  • General Medicine

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