Insights into therapeutic products, preclinical research models and clinical trials in cardiac regenerative and reparative medicine: where are we now and the way ahead. Current opinion paper of the ESC working group on cardiovascular regenerative and reparative medicine.

Great expectations have been set around the clinical potential of regenerative and reparative medicine in the treatment of cardiovascular diseases (i.e., in particular heart failure [HF]). Initial excitement, spurred by encouraging preclinical data, resulted in a rapid translation into clinical research. The sobering outcome of the resulting clinical trials suggests that preclinical testing may have been insufficient to predict clinical outcome. Number of barriers for clinical translation include the inherent variability of the biological products and difficulties to develop potency and quality assays, insufficient rigor of the preclinical research and reproducibility of the results, manufacturing challenges and scientific irregularities reported in the last years. The failure to achieve clinical success led to an increased scrutiny and skepticism as to the clinical readiness of stem cells and gene therapy products among clinicians, industry stakeholders and funding bodies. The present impasse has attracted the attention of some of the most active research groups in the field, which were then summoned to analyze the position of the field and tasked to develop a strategy, to re-visit the undoubtedly promising future of cardiovascular regenerative and reparative medicine, based on lessons learned over the past two decades. During the scientific retreat of the ESC Working Group on Cardiovascular Regenerative and Reparative Medicine (CARE) in November 2018, the most relevant and timely research aspects in regenerative and/or reparative medicine were presented and critically discussed, with the aim to lay out a strategy for the future development of the field. We report herein the main ideas and conclusions of that meeting.