Translational Research in Cardiovascular Repair

Abstract

The international consortium TACTICS (Transnational Alliance for Regenerative Therapies in Cardiovascular Syndromes) has recently addressed key priorities in the field of cell-based therapy for cardiac repair, identifying the efficacy of translational research as one of the main challenges to ultimately improve the quality of life of patients with ischemic disease. Much of the controversy and confusion surrounding cardiac regenerative therapy stems from insufficient rigor in the conduct of preclinical studies, and there is an increasing recognition of a number of problems that undermine its quality that may contribute to translational failure. Here, we introduce well defined stages for preclinical research, and put forth proposals that should promote more rigorous preclinical work, in an effort to improve its quality and translatability. To augment the utility of preclinical research and its translation, it is necessary to (1) improve the quality of preclinical research, (2) promote collaborative efforts, and (3) enhance the sharing of knowledge and protocols. In particular, confirmatory (stage III) preclinical studies should be considered as a preamble to clinical studies and therefore must adhere to their standards of quality (including internal validity, standardization of protocols, and multicenter design). To increase transparency and minimize bias, these studies should be prospectively registered in an independent, open database. Ultimately, these recommendations should be implemented in the daily routine of investigators and in the policies of institutions, journals, and funding agencies.

Therapeutic approaches for cardiac regeneration and repair

“…The lack of sufficient scientific rigour of clinical trials of cardiac regeneration stands as a major challenge for clinical application of cardiac regenerative therapies, because positive outcomes in initial clinical trials, which tended to be performed on a small scale, were often not reproduced in later, well-randomized, large-scale clinical trials. Altogether, study designs in preclinical settings require further refinements, and establishing a more feasible translational path could reduce the risk of clinical translational failure 204 .…”

Echocardiography-guided percutaneous left ventricular intracavitary injection as a cell delivery approach in infarcted mice

“…After two decades of intensive research in the field of cell therapy for heart disease, conclusive demonstration of therapeutic efficacy of the cells is still lacking, and a fundamental understanding of how cell therapy works is still elusive[1, 3, 4, 29-31]. This has led to discussions of changes in the field and search for new paradigms for future research.…”

Multicenter preclinical studies as an innovative method to enhance translation: a systematic review of published studies

“…Translational barriers associated with preclinical research include poor study design and reporting that make reproducibility difficult; biased selection of animal models and small sample sizes which reduces inferential strength; and publication bias which may distort evidence and justification to proceed to first-in-human trials [5, 6, 11]. In order to increase the chance of ‘bench-to-bedside’ translation success, various measures to improve the state of preclinical research have been suggested [12, 13]. One measure is the application of multicenter experimentation in preclinical studies, analogous to what is commonly done in clinical trials [14, 15].…”

“…To improve the process of translation, multiple calls from the biomedical science community have been made to adopt the multicenter preclinical approach [6, 12–14, 16, 17]. Some recent examples have been published that exemplify the successful implementation of this approach [18–20].…”