| Autor: |
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 |
| Předmět: |
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| Zdroj: |
PLoS Neglected Tropical Diseases; 8/27/2020, Vol. 14 Issue 8, p1-22, 22p |
| Abstrakt: |
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/Principal 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. Author summary: Schistosomiasis is the second most prevalent parasitic disease in the world and is caused by the Schistosoma trematode. This disease is characterized by a granulomatous reaction around parasite eggs trapped in the tissues. The liver is one of the most affected organs and can develop severe fibrosis. Praziquantel (PZQ) is the treatment for schistosomiasis and kills the adult the worm; however, inflammation still persists around the eggs in the tissues. Mesenchymal stem cells (MSC) have been extensively studied as an alternative therapy to repair tissues and to stop inflammation due to their potential to differentiate in several cells types (bone, cartilage, fat, tendon, muscle, and marrow stroma), and to interfere with immune responses. This scenario has motivated the authors to investigate the use of MSC extract from adipose tissue (ASC) associated with PZQ to treat schistosomiasis. Briefly, mice were treated with PZQ followed by ASC injection showing significant reduction of the granulomas and normal levels of the enzyme alanine aminotransferase, an indicator of liver damage. These results suggest that ASC has the potential to be used as a novel therapeutic approach to control inflammation following infection by S. mansoni or liver disorders. Although the findings are promising, further studies using the chronic model of schistosomiasis are required to confirm using ASC for schistosomiasis therapy. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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