Towards the standardization of stem cell therapy studies for ischemic heart diseases: Bridging the gap between animal models and the clinical setting

Abstract

Today there is an increasing demand for heart transplantations for patients diagnosed with heart failure. Though, shortage of donors as well as the large number of ineligible patients hurdle such treatment option. This, in addition to the considerable number of transplant rejections, has driven the clinical research towards the field of regenerative medicine. Nonetheless, to date, several stem cell therapies tested in animal models fall by the wayside and when they meet the criteria to clinical trials, subjects often exhibit modest improvements. A main issue slowing down the admission of such therapies in the domain of human trials is the lack of protocol standardization between research groups, which hampers comparison between different approaches as well as the lack of thought regarding the clinical translation. In this sense, given the large amount of reports on stem cell therapy studies in animal models reported in the last 3 years, we sought to evaluate their advantages and limitations towards the clinical setting and provide some suggestions for the forthcoming investigations. We expect, with this review, to start a new paradigm on regenerative medicine, by evoking the debate on how to plan novel stem cell therapy studies with animal models in order to achieve more consistent scientific production and accelerate the admission of stem cell therapies in the clinical setting.

A Rainbow Reporter Tracks Single Cells and Reveals Heterogeneous Cellular Dynamics among Pluripotent Stem Cells and Their Differentiated Derivatives

“…Interestingly, after the first day of culture we saw reductions in cell area that were not accompanied with increases in cell height, which we attribute to the presence of ROCK inhibitor in the first 26 h of culture (day 0 and day 1 time points), which has been shown to promote cell spreading ( Flevaris et al., 2007 , Maldonado et al., 2016 ) without changing cell height ( Nilius et al., 1999 ). Understanding the variability of these cellular phenotypes will be critical to standardize and efficiently manufacture stem cells for cell therapies ( Jossen et al., 2018 , Trindade et al., 2017 ).…”

A Rainbow Reporter Tracks Single Cells and Reveals Heterogeneous Cellular Dynamics among Pluripotent Stem Cells and their Differentiated Derivatives

“…Interestingly, after the first day of culture we saw reductions in cell area that were not accompanied with increases in cell height, which we attribute to the presence of ROCK inhibitor in the first 26 hours of culture (Day0 and Day1 timepoints) which has been shown to promote cell spreading (Flevaris et al, 2007;Maldonado et al, 2016) without changing cell height (Nilius et al, 1999). Understanding the variability of these cellular phenotypes will be critical to standardize and efficiently manufacture stem cells for cell therapies (Trindade et al, 2017;Jossen et al, 2018).…”

Stem Cell Therapy in Heart Diseases – Cell Types, Mechanisms and Improvement Strategies

“…Thus, prospective research should focus on the development of specific responder scores and the identification of prognostic biomarkers to identify patient cohorts who benefit most from distinct SC treatments [526,527]. Thereby, a higher standardization of study designs and the establishment of a global open-access database for the registration and publication of preclinical and clinical trials would greatly improve the comparability and access of obtained data [526,528,529]. …”