Therapeutic efficacy of cardiosphere-derived cells in a transgenic mouse model of non-ischaemic dilated cardiomyopathy

Mohammad A. Aminzadeh, Eleni Tseliou, Baiming Sun, Ke Cheng, Konstantinos Malliaras, Raj R. Makkar, Eduardo Marbán

Research output: Contribution to journalArticle

Abstract

Aim: Cardiosphere-derived cells (CDCs) produce regenerative effects in the post-infarct setting. However, it is unclear whether CDCs are beneficial in non-ischaemic dilated cardiomyopathy (DCM). We tested the effects of CDC transplantation in mice with cardiac-specific Gαq overexpression, which predictably develop progressive cardiac dilation and failure, with accelerated mortality. Methods and results: Wild-type mouse CDCs (105 cells) or vehicle only were injected intramyocardially in 6-, 8-, and 11-week-old Gαq mice. Cardiac function deteriorated in vehicle-treated mice over 3 months of follow-up, accompanied by oxidative stress, inflammation and adverse ventricular remodelling. In contrast, CDCs preserved cardiac function and volumes, improved survival, and promoted cardiomyogenesis while blunting Gαq-induced oxidative stress and inflammation in the heart. The mechanism of benefit is indirect, as long-term engraftment of transplanted cells is vanishingly low. Conclusions: Cardiosphere-derived cells reverse fundamental abnormalities in cell signalling, prevent adverse remodelling, and improve survival in a mouse model of DCM. The ability to impact favourably on disease progression in non-ischaemic heart failure heralds new potential therapeutic applications of CDCs.

Original languageEnglish (US)
Pages (from-to)751-762
Number of pages12
JournalEuropean Heart Journal
Volume36
Issue number12
DOIs
StatePublished - Mar 21 2015
Externally publishedYes

Keywords

  • Cardiomyopathy
  • Cell transplantation
  • Heart failure

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Fingerprint Dive into the research topics of 'Therapeutic efficacy of cardiosphere-derived cells in a transgenic mouse model of non-ischaemic dilated cardiomyopathy'. Together they form a unique fingerprint.

  • Cite this

    Aminzadeh, M. A., Tseliou, E., Sun, B., Cheng, K., Malliaras, K., Makkar, R. R., & Marbán, E. (2015). Therapeutic efficacy of cardiosphere-derived cells in a transgenic mouse model of non-ischaemic dilated cardiomyopathy. European Heart Journal, 36(12), 751-762. https://doi.org/10.1093/eurheartj/ehu196