Increased mitotic rate coincident with transient telomere lengthening resulting from Pim-1 overexpression in cardiac progenitor cells

Christopher T. Cottage, Lauren Neidig, Balaji Sundararaman, Shabana Din, Anya Y. Joyo, Brandi Bailey, Natalie Gude, Nirmala Hariharan, Mark A. Sussman

Research output: Contribution to journalArticle

29 Scopus citations

Abstract

Cardiac regeneration following myocardial infarction rests with the potential of c-kit+ cardiac progenitor cells (CPCs) to repopulate damaged myocardium. The ability of CPCs to reconstitute the heart is restricted by patient age and disease progression. Increasing CPC proliferation, telomere length, and survival will improve the ability of autologous CPCs to be successful in myocardial regeneration. Prior studies have demonstrated enhancement of myocardial regeneration by engineering CPCs to express Pim-1 kinase, but cellular and molecular mechanisms for Pim-1-mediated effects on CPCs remain obscure. We find CPCs rapidly expand following overexpression of cardioprotective kinase Pim-1 (CPCeP), however, increases in mitotic rate are short-lived as late passage CPCePs proliferate similar to control CPCs. Telomere elongation consistent with a young phenotype is observed following Pim-1 modification of CPCeP; in addition, telomere elongation coincides with increased telomerase expression and activity. Interestingly, telomere length and telomerase activity normalize after several rounds of passaging, consistent with the ability of Pim-1 to transiently increase mitosis without resultant oncogenic transformation. Accelerating mitosis in CPCeP without immortalization represents a novel strategy to expand the CPC population in order to improve their therapeutic efficacy.

Original languageEnglish (US)
Pages (from-to)2512-2522
Number of pages11
JournalStem Cells
Volume30
Issue number11
DOIs
StatePublished - Nov 1 2012
Externally publishedYes

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Keywords

  • Cardiac progenitor cell
  • Pim-1
  • Telomerase
  • Telomere

ASJC Scopus subject areas

  • Molecular Medicine
  • Developmental Biology
  • Cell Biology

Cite this

Cottage, C. T., Neidig, L., Sundararaman, B., Din, S., Joyo, A. Y., Bailey, B., Gude, N., Hariharan, N., & Sussman, M. A. (2012). Increased mitotic rate coincident with transient telomere lengthening resulting from Pim-1 overexpression in cardiac progenitor cells. Stem Cells, 30(11), 2512-2522. https://doi.org/10.1002/stem.1211