title: Therapeutic efficacy of cardiosphere-derived cells in a transgenic mouse model of non-ischaemic dilated cardiomyopathy.
abstract: OBJECTIVE
  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.
  
  
  RESULTS
  Wild-type mouse CDCs (10(5) 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.
authors.affiliation: Cedars-Sinai Heart Institute, 8700 Beverly Boulevard, Los Angeles, CA 90048, USA.
authors.forename: Mohammad A
authors.initials: MA
authors.lastname: Aminzadeh
authors.affiliation: Cedars-Sinai Heart Institute, 8700 Beverly Boulevard, Los Angeles, CA 90048, USA.
authors.forename: Eleni
authors.initials: E
authors.lastname: Tseliou
authors.affiliation: Cedars-Sinai Heart Institute, 8700 Beverly Boulevard, Los Angeles, CA 90048, USA.
authors.forename: Baiming
authors.initials: B
authors.lastname: Sun
authors.affiliation: Cedars-Sinai Heart Institute, 8700 Beverly Boulevard, Los Angeles, CA 90048, USA.
authors.forename: Ke
authors.initials: K
authors.lastname: Cheng
authors.affiliation: Cedars-Sinai Heart Institute, 8700 Beverly Boulevard, Los Angeles, CA 90048, USA.
authors.forename: Konstantinos
authors.initials: K
authors.lastname: Malliaras
authors.affiliation: Cedars-Sinai Heart Institute, 8700 Beverly Boulevard, Los Angeles, CA 90048, USA.
authors.forename: Raj R
authors.initials: RR
authors.lastname: Makkar
authors.affiliation: Cedars-Sinai Heart Institute, 8700 Beverly Boulevard, Los Angeles, CA 90048, USA Eduardo.Marban@cshs.org.
authors.forename: Eduardo
authors.initials: E
authors.lastname: Marbán
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology; D050882:CREB-Binding Protein / Q000378:metabolism; D002311:Cardiomyopathy, Dilated / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D002454:Cell Differentiation; D019070:Cell Lineage; D004195:Disease Models, Animal; D004317:Doxorubicin / Q000494:pharmacology; D005355:Fibrosis; D006085:Graft Survival; D006333:Heart Failure / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D015552:Injections, Intralesional; D008297:Male; D008822:Mice, Transgenic; D009205:Myocarditis / Q000503:physiopathology; D009206:Myocardium / Q000473:pathology; D032383:Myocytes, Cardiac / Q000637:transplantation*; D018384:Oxidative Stress / Q000502:physiology; D011493:Protein Kinase C / Q000378:metabolism; D015398:Signal Transduction; D033581:Stem Cell Transplantation / Q000379:methods*; D020257:Ventricular Remodeling / Q000502:physiology
chemical_list: D004317:Doxorubicin; D050882:CREB-Binding Protein; C494364:Crebbp protein, mouse; C089212:protein kinase D; D011493:Protein Kinase C
keywords: Cardiomyopathy; Cell transplantation; Heart failure