Liver damage in schistosomiasis is reduced by adipose tissue-derived stem cell therapy after praziquantel treatment.

<h4>Background</h4>In view of the potential immunosuppressive and regenerative properties of mesenchymal stem cells (MSC), we investigated whether transplantation of adipose tissue-derived stem cells (ASC) could be used to control the granulomatous reaction in the liver of mice infected...

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Main Authors: Vitor Hugo Simões Miranda, Talita Rocha Gomes, Dirli Emerick Eller, Lorena de Cássia Neres Ferraz, Ana Thereza Chaves, Kelly Alves Bicalho, Carlos Eduardo Calzavara Silva, Alexander Birbrair, Marcelo Antônio Pascoal Xavier, Alfredo Miranda de Goes, Rodrigo Corrêa-Oliveira, Érica Alessandra Rocha Alves, Adriana Bozzi
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2020-08-01
Series:PLoS Neglected Tropical Diseases
Online Access:https://doi.org/10.1371/journal.pntd.0008635
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spelling doaj-7959d0ab9b584983ba53552645a1411f2021-03-03T08:25:03ZengPublic Library of Science (PLoS)PLoS Neglected Tropical Diseases1935-27271935-27352020-08-01148e000863510.1371/journal.pntd.0008635Liver damage in schistosomiasis is reduced by adipose tissue-derived stem cell therapy after praziquantel treatment.Vitor Hugo Simões MirandaTalita Rocha GomesDirli Emerick EllerLorena de Cássia Neres FerrazAna Thereza ChavesKelly Alves BicalhoCarlos Eduardo Calzavara SilvaAlexander BirbrairMarcelo Antônio Pascoal XavierAlfredo Miranda de GoesRodrigo Corrêa-OliveiraÉrica Alessandra Rocha AlvesAdriana Bozzi<h4>Background</h4>In view of the potential immunosuppressive and regenerative properties of mesenchymal stem cells (MSC), we investigated whether transplantation of adipose tissue-derived stem cells (ASC) could be used to control the granulomatous reaction in the liver of mice infected with Schistosoma mansoni after Praziquantel (PZQ) treatment.<h4>Methodology/prinicpal findings</h4>C57BL/6 mice infected with S. mansoni were treated with PZQ and transplanted intravenously with ASC from uninfected mice. Liver morpho-physiological and immunological analyses were performed. The combined PZQ/ASC therapy significantly reduced the volume of hepatic granulomas, as well as liver damage as measured by ALT levels. We also observed that ASC accelerated the progression of the granulomatous inflammation to the advanced/curative phase. The faster healing interfered with the expression of CD28 and CTLA-4 molecules in CD4+ T lymphocytes, and the levels of IL-10 and IL-17 cytokines, mainly in the livers of PZQ/ASC-treated mice.<h4>Conclusions</h4>Our results show that ASC therapy after PZQ treatment results in smaller granulomas with little tissue damage, suggesting the potential of ASC for the development of novel therapeutic approaches to minimize hepatic lesions as well as a granulomatous reaction following S. mansoni infection. Further studies using the chronic model of schistosomiasis are required to corroborate the therapeutic use of ASC for schistosomiasis.https://doi.org/10.1371/journal.pntd.0008635
collection DOAJ
language English
format Article
sources DOAJ
author Vitor Hugo Simões Miranda
Talita Rocha Gomes
Dirli Emerick Eller
Lorena de Cássia Neres Ferraz
Ana Thereza Chaves
Kelly Alves Bicalho
Carlos Eduardo Calzavara Silva
Alexander Birbrair
Marcelo Antônio Pascoal Xavier
Alfredo Miranda de Goes
Rodrigo Corrêa-Oliveira
Érica Alessandra Rocha Alves
Adriana Bozzi
spellingShingle Vitor Hugo Simões Miranda
Talita Rocha Gomes
Dirli Emerick Eller
Lorena de Cássia Neres Ferraz
Ana Thereza Chaves
Kelly Alves Bicalho
Carlos Eduardo Calzavara Silva
Alexander Birbrair
Marcelo Antônio Pascoal Xavier
Alfredo Miranda de Goes
Rodrigo Corrêa-Oliveira
Érica Alessandra Rocha Alves
Adriana Bozzi
Liver damage in schistosomiasis is reduced by adipose tissue-derived stem cell therapy after praziquantel treatment.
PLoS Neglected Tropical Diseases
author_facet Vitor Hugo Simões Miranda
Talita Rocha Gomes
Dirli Emerick Eller
Lorena de Cássia Neres Ferraz
Ana Thereza Chaves
Kelly Alves Bicalho
Carlos Eduardo Calzavara Silva
Alexander Birbrair
Marcelo Antônio Pascoal Xavier
Alfredo Miranda de Goes
Rodrigo Corrêa-Oliveira
Érica Alessandra Rocha Alves
Adriana Bozzi
author_sort Vitor Hugo Simões Miranda
title Liver damage in schistosomiasis is reduced by adipose tissue-derived stem cell therapy after praziquantel treatment.
title_short Liver damage in schistosomiasis is reduced by adipose tissue-derived stem cell therapy after praziquantel treatment.
title_full Liver damage in schistosomiasis is reduced by adipose tissue-derived stem cell therapy after praziquantel treatment.
title_fullStr Liver damage in schistosomiasis is reduced by adipose tissue-derived stem cell therapy after praziquantel treatment.
title_full_unstemmed Liver damage in schistosomiasis is reduced by adipose tissue-derived stem cell therapy after praziquantel treatment.
title_sort liver damage in schistosomiasis is reduced by adipose tissue-derived stem cell therapy after praziquantel treatment.
publisher Public Library of Science (PLoS)
series PLoS Neglected Tropical Diseases
issn 1935-2727
1935-2735
publishDate 2020-08-01
description <h4>Background</h4>In view of the potential immunosuppressive and regenerative properties of mesenchymal stem cells (MSC), we investigated whether transplantation of adipose tissue-derived stem cells (ASC) could be used to control the granulomatous reaction in the liver of mice infected with Schistosoma mansoni after Praziquantel (PZQ) treatment.<h4>Methodology/prinicpal findings</h4>C57BL/6 mice infected with S. mansoni were treated with PZQ and transplanted intravenously with ASC from uninfected mice. Liver morpho-physiological and immunological analyses were performed. The combined PZQ/ASC therapy significantly reduced the volume of hepatic granulomas, as well as liver damage as measured by ALT levels. We also observed that ASC accelerated the progression of the granulomatous inflammation to the advanced/curative phase. The faster healing interfered with the expression of CD28 and CTLA-4 molecules in CD4+ T lymphocytes, and the levels of IL-10 and IL-17 cytokines, mainly in the livers of PZQ/ASC-treated mice.<h4>Conclusions</h4>Our results show that ASC therapy after PZQ treatment results in smaller granulomas with little tissue damage, suggesting the potential of ASC for the development of novel therapeutic approaches to minimize hepatic lesions as well as a granulomatous reaction following S. mansoni infection. Further studies using the chronic model of schistosomiasis are required to corroborate the therapeutic use of ASC for schistosomiasis.
url https://doi.org/10.1371/journal.pntd.0008635
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