ABSTRACT
Heart failure is a life-threatening and costly ailment characterized by structural and functional impairment of the heart. Despite major advances in understanding protein-mediated transcriptional control and signaling pathways that underlie the cellular and interstitial alterations of heart failure, significant therapeutical breakthroughs for innovative treatments of this disease are still missing. The recent extensive profiling of the mammalian transcriptome has revealed a large number of long non-coding RNAs (lncRNAs) that play a diversity of important regulatory roles in gene expression. In here, we focus on a recent work by Ounzain and colleagues comprising genome-wide profiling of the cardiac transcriptome after myocardial infarction with an emphasis on the identification of novel heart-specific lncRNAs.
ABSTRACT
RATIONALE: In regenerative therapy for ischemic heart disease, use of both autologous and allogeneic stem cells has been investigated. Autologous cell can be applied without immunosuppression, but availability is restricted, and cells have been exposed to risk factors and aging. Allogeneic cell therapy enables preoperative production of potent cell lines and immediate availability of cell products, allowing off-the-shelf therapy. It is unknown which cell source is preferred with regard to improving cardiac function. OBJECTIVE: We performed a meta-analysis of preclinical data of cell therapy for ischemic heart disease. METHODS AND RESULTS: We conducted a systematic literature search to identify publications describing controlled preclinical trials of unmodified stem cell therapy in large animal models of myocardial ischemia. Data from 82 studies involving 1415 animals showed a significant improvement in mean left ventricular ejection fraction in treated compared with control animals (8.3%, 95% confidence interval, 7.1-9.5; P<0.001). Meta-regression revealed a similar difference in left ventricular ejection fraction in autologous (8.8%, 95% confidence interval, 7.3-10.3; n=981) and allogeneic (7.3%, 95% confidence interval, 4.4-10.2, n=331; P=0.3) cell therapies. CONCLUSIONS: Autologous and allogeneic cell therapy for ischemic heart disease show a similar improvement in left ventricular ejection fraction in large animal models of myocardial ischemia, compared with placebo. These results are important for the design of future clinical trials.
