Preclinical stem cell therapy in Chagas Disease: Perspectives for future research

Abstract

Chagas cardiomyopathy still remains a challenging problem that is responsible for high morbidity and mortality in Central and Latin America. Chagas disease disrupts blood microcirculation via various autoimmune mechanisms, causing loss of cardiomyocytes and severe impairment of heart function. Different cell types and delivery approaches in Chagas Disease have been studied in both preclinical models and clinical trials. The main objective of this article is to clarify the reasons why the benefits that have been seen with cell therapy in preclinical models fail to translate to the clinical setting. This can be explained by crucial differences between the cellular types and pathophysiological mechanisms of the disease, as well as the differences between human patients and animal models. We discuss examples that demonstrate how the results from preclinical trials might have overestimated the efficacy of myocardial regeneration therapies. Future research should focus, not only on studying the best cell type to use but, very importantly, understanding the levels of safety and cellular interaction that can elicit efficient therapeutic effects in human tissue. Addressing the challenges associated with future research may ensure the success of stem cell therapy in improving preclinical models and the treatment of Chagas disease.

The Rising Role of Mesenchymal Stem Cells in the Treatment of Various Infectious Complications

“…The available and future therapies of Chagas disease include: treatment of arrhythmias and heart failure, antiparasitic therapy, resynchronization treatment, heart transplantation, and stem cell therapies [2,90,91,93,95]. In patients with chronic Chagas CMP and cardiac failure, conventional pharmacologic therapies are limited by being not always effective, thus rendering the disease incurable [90,91,96].…”

“…Heart transplantation may occasionally be needed but the procedure has a number of problems including: shortage of donors, high costs, and complications of long-term immunosuppressive therapies administered to recipients of heart transplants [90,95].…”

“…Different stem cell types and delivery approaches have been used in both preclinical models as well as clinical trials with the aim of improving cardiac function and reversing complications [95]. In animal models, stem cell therapies have shown reductions in: right ventricular dilatation, and inflammatory infiltrates as well as fibrosis [91,93].…”

“…Transplantation of MSCs has shown clinical efficacy in animal or mouse models but studies in humans have not shown equivalent success due to a number of challenges that need to be overcome [2,91,93,95,98]. In animal models of chronic Chagas CMP, cardiac MSCs have been shown to exert protective effects by decreasing the degrees of fibrosis and inflammatory infiltrates in the affected myocardium [99].…”

Hydroxamic acid derivatives: a promising scaffold for rational compound optimization in Chagas disease

“…Also it is important to highlight that the T. cruzi polyparasitism and co-infection with other pathogens may interfere with the failure of the present therapeutic interventions 11 . The failure of promising drugs undergoing clinical trials 12 and also the unsuccessful stem cell therapy 13 reinforce the need for new strategies in the treatment and management of Chagas' disease 14 . These strategies should include an analysis of the advantage of combination therapy 15 and eventual benefits from vaccine development 16 , as well as the identification of new drug targets and biomarkers to monitor the treatment response and cure prediction.…”