Cell therapies for Chagas disease

Carvalho, Adriana Bastos; Goldenberg, Regina Coeli dos Santos; Carvalho, Antônio Carlos Campos de

doi:10.1016/j.jcyt.2017.07.014

Cited by 11 publications

(8 citation statements)

References 46 publications

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“…The use of cell therapies has been investigated in a number of cardiac diseases, including chronic Chagas disease, but currently no efficient treatment has been established for clinical practice ( 18 , 19 ). Previous studies have shown improvements after MSC-based therapy in the mouse model of Chagas disease ( 11 – 14 , 20 ).…”

Section: Discussionmentioning

confidence: 99%

Granulocyte-Colony Stimulating Factor-Overexpressing Mesenchymal Stem Cells Exhibit Enhanced Immunomodulatory Actions Through the Recruitment of Suppressor Cells in Experimental Chagas Disease Cardiomyopathy

et al. 2018

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Genetic modification of mesenchymal stem cells (MSCs) is a promising strategy to improve their therapeutic effects. Granulocyte-colony stimulating factor (G-CSF) is a growth factor widely used in the clinical practice with known regenerative and immunomodulatory actions, including the mobilization of regulatory T cells (Tregs) and myeloid-derived suppressor cells (MDSCs). Here we evaluated the therapeutic potential of MSCs overexpressing G-CSF (MSC_G-CSF) in a model of inflammatory cardiomyopathy due to chronic Chagas disease. C57BL/6 mice were treated with wild-type MSCs, MSC_G-CSF, or vehicle (saline) 6 months after infection with Trypanosoma cruzi. Transplantation of MSC_G-CSF caused an increase in the number of circulating leukocytes compared to wild-type MSCs. Moreover, G-CSF overexpression caused an increase in migration capacity of MSCs to the hearts of infected mice. Transplantation of either MSCs or MSC_G-CSF improved exercise capacity, when compared to saline-treated chagasic mice. MSC_G-CSF mice, however, were more potent than MSCs in reducing the number of infiltrating leukocytes and fibrosis in the heart. Similarly, MSC_G-CSF-treated mice presented significantly lower levels of inflammatory mediators, such as IFNγ, TNFα, and Tbet, with increased IL-10 production. A marked increase in the percentage of Tregs and MDSCs in the hearts of infected mice was seen after administration of MSC_G-CSF, but not MSCs. Moreover, Tregs were positive for IL-10 in the hearts of T. cruzi-infected mice. In vitro analysis showed that recombinant hG-CSF and conditioned medium of MSC_G-CSF, but not wild-type MSCs, induce chemoattraction of MDSCs in a transwell assay. Finally, MDSCs purified from hearts of MSC_G-CSF transplanted mice inhibited the proliferation of activated splenocytes in a co-culture assay. Our results demonstrate that G-CSF overexpression by MSCs potentiates their immunomodulatory effects in our model of Chagas disease and suggest that mobilization of suppressor cell populations such as Tregs and MDSCs as a promising strategy for the treatment of chronic Chagas disease. Finally, our results reinforce the therapeutic potential of genetic modification of MSCs, aiming at increasing their paracrine actions.

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Section: Discussionmentioning

confidence: 99%

Granulocyte-Colony Stimulating Factor-Overexpressing Mesenchymal Stem Cells Exhibit Enhanced Immunomodulatory Actions Through the Recruitment of Suppressor Cells in Experimental Chagas Disease Cardiomyopathy

et al. 2018

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“…Another factor to be considered is the number of cells used in the therapeutic scheme. To use in humans a dose equivalent to that used in studies with mice, it would be necessary to transplant 3.5 billion cells, while in the study performed on humans the treatment was done with 100 to 250 million cells ( Carvalho et al., 2017 ).…”

Section: Immunomodulatory Agents and CCCmentioning

confidence: 99%

Immunomodulation for the Treatment of Chronic Chagas Disease Cardiomyopathy: A New Approach to an Old Enemy

Santos

Silva

Reis

et al. 2021

Front. Cell. Infect. Microbiol.

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Chagas disease is a parasitic infection caused by the intracellular protozoan Trypanosoma cruzi. Chronic Chagas cardiomyopathy (CCC) is the most severe manifestation of the disease, developed by approximately 20-40% of patients and characterized by occurrence of arrhythmias, heart failure and death. Despite having more than 100 years of discovery, Chagas disease remains without an effective treatment, especially for patients with CCC. Since the pathogenesis of CCC depends on a parasite-driven systemic inflammatory profile that leads to cardiac tissue damage, the use of immunomodulators has become a rational alternative for the treatment of CCC. In this context, different classes of drugs, cell therapies with dendritic cells or stem cells and gene therapy have shown potential to modulate systemic inflammation and myocarditis in CCC models. Based on that, the present review provides an overview of current reports regarding the use of immunomodulatory agents in treatment of CCC, bringing the challenges and future directions in this field.

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“…Following the initial success with mouse-models (reviewed by Carvalho et al[63]) the next step was to evaluate whether such results could be achieved during human infection. The first clinal trial took place on a 52-year-old man suffering of heart failure due to T. cruzi infection[64].…”

Section: Stem Cell and Parasite Therapiesmentioning

confidence: 99%

Unexpected encounter of the parasitic kind

Matthews

Noulin

2019

WJSC

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Both parasitology and stem cell research are important disciplines in their own right. Parasites are a real threat to human health causing a broad spectrum of diseases and significant annual rates morbidity and mortality globally. Stem cell research, on the other hand, focuses on the potential for regenerative medicine for a range of diseases including cancer and regenerative therapies. Though these two topics might appear distant, there are some “unexpected encounters”. In this review, we summarise the various links between parasites and stem cells. First, we discuss how parasites’ own stem cells represent interesting models of regeneration that can be translated to human stem cell regeneration. Second, we explore the interactions between parasites and host stem cells during the course of infection. Third, we investigate from a clinical perspective, how stem cell regeneration can be exploited to help circumvent the damage induced by parasitic infection and its potential to serve as treatment options for parasitic diseases in the future. Finally, we discuss the importance of screening for pathogens during organ transplantation by presenting some clinical cases of parasitic infection following stem cell therapy.

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Cell therapies for Chagas disease

Cited by 11 publications

References 46 publications

Granulocyte-Colony Stimulating Factor-Overexpressing Mesenchymal Stem Cells Exhibit Enhanced Immunomodulatory Actions Through the Recruitment of Suppressor Cells in Experimental Chagas Disease Cardiomyopathy

Granulocyte-Colony Stimulating Factor-Overexpressing Mesenchymal Stem Cells Exhibit Enhanced Immunomodulatory Actions Through the Recruitment of Suppressor Cells in Experimental Chagas Disease Cardiomyopathy

Immunomodulation for the Treatment of Chronic Chagas Disease Cardiomyopathy: A New Approach to an Old Enemy

Unexpected encounter of the parasitic kind

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