Clinical trials of myocardium injury cell therapy

Abstract

The high mortality rate from heart disease requires the development of new therapeutic approaches. Traditional treatments can provide a compensatory effect, improve the patient's quality of life, but not eliminate myocardial loss. Preclinical studies indicate that the regeneration of cardiac tissue can be stimulated through transplantation of stem and progenitor cells. The review describes clinical trials of myocardial injury therapy using regional stem cells, progenitor cells, and cells differentiated from ESC/iPSCs. The results of clinical studies have confirmed the safety and availability of cell therapy for myocardial injury. However, insufficient knowledge of the mechanisms of action of transplanted cells on the myocardium and the rapid deployment of clinical trials initiated by the success of preclinical trials made it possible to observe, at best, only a moderate therapeutic effect. In studies using regional stem cells, it was not possible to reliably confirm their ability to differentiate into cardiomyocytes and integrate into the myocardium, and the observed improvements in heart function are associated with paracrine signaling. Cardiac ESC/iPSC derivatives are more suitable for the restoration of the lost myocardium, but since the number of clinical trials with these types of cells is still small, additional studies are required to confirm their safety and efficacy. When developing the design of future clinical trials of cell therapy, it is necessary to strictly take into account the mechanism of cell action, the pathophysiology of the disease, and select the optimal set of endpoints. The experience of the conducted research leads to an understanding of the need to develop personalized cell therapy, according to which the choice of the source of cells and the route of administration should be based on the individual characteristics of the patient. The growing number of clinical trials and the active study of the mechanisms of action of transplanted cells on damaged myocardium suggest that this type of cell therapy has a chance to enter clinical practice in the near future. Received 4 October 2021. Revised 13 December 2021. Accepted 20 December 2021. Funding: The study did not have sponsorship. Conflict of interest: Authors declare no conflict of interest. Contribution of the authors: The authors contributed equally to this article.