Cardiomyocyte Cell Cycle, Renewal and Isolation

Research output: ThesisDoctoral Thesis (compilation)

Abstract

Heart disease results from the loss of cardiomyocytes following myocardial damage and is a leading cause of death worldwide. Stimulating the endogenous regeneration of cardiomyocytes or isolating them from in vitro culture is an attractive therapeutic strategy. In paper I, the focus is on the cellular growth patterns of murine cardiomyocytes under steady-state conditions. The turnover of cardiomyocytes was accurately established and key gene expression patterns associated with developmentally distinct periods of cardiomyocyte growth and turnover were identified. There was no significant generation of cardiomyocytes in the adult mouse heart. In paper II, the focus is on turnover of human cardiomyocytes . Taking advantage of the integration of 14C generated by nuclear bomb tests during the Cold War into DNA, we were able to accurately establish the age of cardiomyocytes in humans. Through mathematical modeling it was established that cardiomyocytes are renewed at a rate of approximately 1% per year at the age of 20 and 0.4% at the age of 75. In papers III and IV, the focus was the development of isolation strategies for embryonic (paper III & IV) and more mature cardiomyocytes (paper IV). We establish a non-genetic FACS based technique utilizing the surface marker VCAM-1, facilitating the enrichment of embryonic cardiomyocytes (paper III). Additional surface markers are assayed for their potential to isolate cardiomyocytes from other time-points in paper IV.
This thesis provides new knowledge in the field of cardiomyocyte kinetics and mitotic activity. In addition we have identified key genes involved in cell cycle control in cardiomyocytes, which are potential candidates for therapeutic manipulation. We have also established a non-genetic FACS based purification method for embryonic cardiomyocytes. Any potential cellular therapy for heart disease involving cardiomyocytes would require the elimination of contaminating non-myocyte cells. A strategy that facilitates a non-genetic method of isolating embryonic cardiomyocytes would also be a powerful tool for the study of such cells.

Details

Authors
  • Stuart Walsh
Research areas and keywords

Subject classification (UKÄ)

  • Cell and Molecular Biology

Keywords

  • binucleation, Cardiomyocytes, surface marker, troponin-T, mitosis, microarray, cell cycle, FACS
Original languageEnglish
QualificationDoctor
Awarding Institution
Supervisors/Assistant supervisor
  • Stefan Jovinge, Supervisor
  • Sten Eirik W Jacobsen, Supervisor
Award date2010 Apr 23
Publisher
  • Cardiovascular Laboratory, Center for Stem Cell Biology, Lund
Print ISBNs978-91-86443-59-7
Publication statusPublished - 2010
Publication categoryResearch

Bibliographic note

Defence details Date: 2010-04-23 Time: 14:00 Place: Segerfalk lecture hall, BMC A10, Lund External reviewer(s) Name: Wu, Sean Title: M.D. Ph.D. Affiliation: Cardiovascular Research Center, Massachusetts General Hospital (MGH), Harvard University, Boston, USA --- The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Hematopoietic Stem Cell Laboratory (013022012)

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Related research output

Stuart Walsh, Annica Pontén, Bernd K Fleischmann & Stefan Jovinge, 2010, In: Cardiovascular Research. 86, 3, p. 365-373

Research output: Contribution to journalArticle

Olaf Bergmann, Ratan D. Bhardwaj, Samuel Bernard, Sofia Zdunek, Fanie Barnabe-Heider, Stuart Walsh, Joel Zupicich, Kanar Alkass, Bruce A. Buchholz, Henrik Druid, Stefan Jovinge & Jonas Frisen, 2009, In: Science. 324, 5923, p. 98-102

Research output: Contribution to journalArticle

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