Pursuing meaningful end-points for stem cell therapy assessment in ischemic cardiac disease

Abstract

Despite optimal interventional and medical therapy, ischemic heart disease is still an important cause of morbidity and mortality worldwide. Although not included in standard of care rehabilitation, stem cell therapy (SCT) could be a solution for prompting cardiac regeneration. Multiple studies have been published from the beginning of SCT until now, but overall no unanimous conclusion could be drawn in part due to the lack of appropriate end-points. In order to appreciate the impact of SCT, multiple markers from different categories should be considered: Structural, biological, functional, physiological, but also major adverse cardiac events or quality of life. Imaging end-points are among the most used - especially left ventricle ejection fraction (LVEF) measured through different methods. Other imaging parameters are infarct size, myocardial viability and perfusion. The impact of SCT on all of the aforementioned end-points is controversial and debatable. 2D-echocardiography is widely exploited, but new approaches such as tissue Doppler, strain/strain rate or 3D-echocardiography are more accurate, especially since the latter one is comparable with the MRI gold standard estimation of LVEF. Apart from the objective parameters, there are also patient-centered evaluations to reveal the benefits of SCT, such as quality of life and performance status, the most valuable from the patient point of view. Emerging parameters investigating molecular pathways such as non-coding RNAs or inflammation cytokines have a high potential as prognostic factors. Due to the disadvantages of current techniques, new imaging methods with labelled cells tracked along their lifetime seem promising, but until now only pre-clinical trials have been conducted in humans. Overall, SCT is characterized by high heterogeneity not only in preparation, administration and type of cells, but also in quantification of therapy effects.

Keywords: Stem cell therapy; Cardiac imaging techniques; Ischemic cardiac disease; Cardiac regeneration; End-points

Core tip: Although multiple studies have been published on stem cell therapy (SCT) in ischemic cardiac disease, no universal conclusion regarding its clinical efficacy has been given in part due to the lack of appropriate end-points. A rightful appreciation of SCT impact should be made considering multiple parameters from diverse categories, either objective - evaluating structural and biological functions, or subjective - patient orientated impacting daily quality of life. Current end-points, but also novel parameters investigating molecular pathways and new imaging methods with labelled cells genetically modified are being analytically discussed in this review, disclosing high heterogeneity in SCT efficacy assessment.