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The Cardiac Side Population is Dynamic during the Progression of Cardiomyopathy in the mdx Model of DMD

Lookup NU author(s): Dr Annette Meeson, Dr Steven Laval, Dr Andrew OwensORCiD, Dr Gavin RichardsonORCiD


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Regardless of the pathology, heart failure is associated with a reduction in the total number of viable cardiomyocytes but there is little known regarding how cardiac stem cell populations respond to chronic cardiomyocyte loss. In the mdx mouse model of Duchenne muscular dystrophy myocytes are lost throughout life from both skeletal and cardiac muscle. In skeletal muscle regeneration maintains muscle function in younger animals but this requires continued replenishment from resident stem cells. Dysfunction of stem cell populations is associated with accelerated disease progression as demonstrated by young mice lacking telomerase activity (which maintains telomeres in stem cell populations, allowing extended self-renewal) having an exacerbated disease phenotype. We are investigating whether similar processes occur in the heart. The cardiac side population (CSP) has been demonstrated to be capable of self-renewal, differentiate in vitro to form functionally mature cardiomyocytes and, following transplantation, contribute to the formation of multiple cardiac cell types including cardiomyocytes. We have identified a significant ~5-fold increase in the number of cardiac side population (CSP) cells in the hearts of 13 week mdx mice. This not maintained in the older animals and by 30 weeks old no difference in CSP size was observed and the relative number of this stem cell population continued to decline as dilated cardiomyopathy developed. We crossed mdx mice with mTert-GFP reporter mice to study telomerase activity in the mdx heart. At 13 weeks there was a significant increase both in the total number of mTert-GFP expressing cells and the number mTert-GFP cell within the CSP. Suggesting this mTert-GFP expression was associated with cardiomyocyte renewal, mTert-GFP cells co-expressing cardiac transcription factors were also increased. Once again the increase in these cell populations was not observed in the older mdx hearts. We suggest that the increase in stem cell activity is related to cardiomyocyte replenishment in young mdx animals and, as in skeletal muscle, progression is related to an exhaustion of the cardiac regenerative potential. Further fate-mapping studies will provide more definitive evidence of cardiomyocyte renewal in the mdx heart.

Publication metadata

Author(s): Meeson AP, Laval SH, Owens WA, Richardson GD

Editor(s): N. Rosenthal, B. Graham, S. Dimmeler, D. Stainier

Publication type: Conference Proceedings (inc. Abstract)

Publication status: Published

Conference Name: EMBO/EMBL: Cardiac Biology - From Development to Regenerative Medicine

Year of Conference: 2013