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Increased mitotic rate coincident with transient telomere lengthening resulting from pim-1 overexpression in cardiac progenitor cells.
- Source :
-
Stem cells (Dayton, Ohio) [Stem Cells] 2012 Nov; Vol. 30 (11), pp. 2512-22. - Publication Year :
- 2012
-
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.<br /> (Copyright © 2012 AlphaMed Press.)
- Subjects :
- Animals
Cardiotoxins pharmacology
Cell Proliferation
Cell Survival
Cells, Cultured
Doxorubicin pharmacology
Enzyme Activation
Gene Expression
Green Fluorescent Proteins biosynthesis
Green Fluorescent Proteins genetics
Mice
Phosphorylation
Protein Binding
Protein Interaction Mapping
Protein Processing, Post-Translational
Proto-Oncogene Proteins c-myc antagonists & inhibitors
Proto-Oncogene Proteins c-myc metabolism
Proto-Oncogene Proteins c-pim-1 genetics
Regenerative Medicine
Stem Cells enzymology
Stem Cells metabolism
Telomerase metabolism
Thiazoles pharmacology
Mitosis
Myocardium cytology
Proto-Oncogene Proteins c-pim-1 metabolism
Stem Cells physiology
Telomere Homeostasis drug effects
Subjects
Details
- Language :
- English
- ISSN :
- 1549-4918
- Volume :
- 30
- Issue :
- 11
- Database :
- MEDLINE
- Journal :
- Stem cells (Dayton, Ohio)
- Publication Type :
- Academic Journal
- Accession number :
- 22915504
- Full Text :
- https://doi.org/10.1002/stem.1211