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World J Transplant. Dec 24, 2013; 3(4): 119-126
Published online Dec 24, 2013. doi: 10.5500/wjt.v3.i4.119
Preclinical stem cell therapy in Chagas Disease: Perspectives for future research
Katherine Athayde Teixeira de Carvalho, Eltyeb Abdelwahid, Reginaldo Justino Ferreira, Ana Carolina Irioda, Luiz Cesar Guarita-Souza
Katherine Athayde Teixeira de Carvalho, Ana Carolina Irioda, Cell Therapy and Biotechnology in Regenerative Medicine Research Group, Pequeno Príncipe Faculty, Pelé Pequeno Príncipe Institute, Curitiba 80250-200, Paraná, Brazil
Katherine Athayde Teixeira de Carvalho, Reginaldo Justino Ferreira, Bioprocess Engineering and Biotechnology Department, Federal University of Paraná, Curitiba 81531-970, Paraná, Brazil
Eltyeb Abdelwahid, CBRC, Massachusetts General Hospital/Harvard Medical School, Charlestown, Ma 02129, United States
Reginaldo Justino Ferreira, Federal University of Technology, Curitiba 80230-901, Paraná, Brazil
Luiz Cesar Guarita-Souza, Experimental Laboratory of Institute of Biological and Health Sciences of Pontifical Catholic University of Parana, Curitiba 80215-901, Paraná, Brazil
Author contributions: de Carvalho KAT proposed the review, analyzed the data; Irioda AC collected the data; de Carvalho KAT, Abdelwahid E and Guarita-Souza LC wrote the manuscript; Ferreira RJ performed the references; de Carvalho KAT edited the manuscript.
Correspondence to: Katherine Athayde Teixeira de Carvalho, Professor, MD, PhD, Cell Therapy and Biotechnology in Regenerative Medicine Research Group, Pequeno Príncipe Faculty, Pelé Pequeno Príncipe Research Institute, Av. Siva Jardim 1632, Curitiba 80250-200, Paraná, Brazil. katherinecarv@gmail.com
Telephone: +55-41-33101719 Fax: +55-41-33221446
Received: August 29, 2013
Revised: September 16, 2013
Accepted: October 18, 2013
Published online: December 24, 2013
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.

Keywords: Chagas Disease, Preclinical, Stem cell, Therapy, Co-cultured, Translation, Pathophysiologie, Myoblasts

Core tip: The manuscript discusses examples that demonstrate how the results from preclinical trials might have overestimated the efficacy of myocardial regeneration with cell therapies, particularly in Chagas Disease and addressing the challenges associated with future research. The failure of cell therapy 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.