PLoS neglected tropical diseases · 2020
Liver damage in schistosomiasis is reduced by adipose tissue-derived stem cell therapy after praziquantel treatment.
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Miranda Vitor Hugo Simões, Gomes Talita Rocha, Eller Dirli Emerick, Ferraz Lorena de Cássia Neres, Chaves Ana Thereza, Bicalho Kelly Alves, Silva Carlos Eduardo Calzavara, Birbrair Alexander, Pascoal Xavier Marcelo Antônio, de Goes Alfredo Miranda, Corrêa-Oliveira Rodrigo, Alves Érica Alessandra Rocha, Bozzi Adriana
Аннотация
BACKGROUND: 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.
METHODOLOGY/PRINICPAL FINDINGS: 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.
CONCLUSIONS: 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.
METHODOLOGY/PRINICPAL FINDINGS: 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.
CONCLUSIONS: 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.