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

Abstract

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.

Vaccination against the HDL receptor of S. japonicum inhibits egg embryonation and prevents fatal hepatic complication in rabbit model

“…The most serious, intractable and sometimes fatal complication is granulomatosis and fibrosis of the liver caused by the embolized eggs as they are ectopically matured to embryonation [2][3][4]. Although the current control measures based on mass drug (praziquantel) administration are effective in killing adult schistosome worms [17,18], the sustained pathology due to mature eggs that have already been laid cannot be overlooked [19,20]. Hence, there is an urgent need to develop any egg-targeting strategies against pathology induced by schistosome infection.…”

Stem cells therapy research for the treatment of parasitic infections

“…Additionally the MSCs were used, in combination with praziquantel, to treat S. japonicum infection in a mouse model and the treatment resulted in smaller hepatic granulomas with little tissue damage [19] . Later, Miranda et al [20] confirmed that also S. mansoni infected-mice treated with combined praziquantel and ASC had smaller granulomas and less tissue damage [20] .…”

Stem Cell-Derived Exosome as Potential Therapeutics for Microbial Diseases

“…However, there are limited therapeutic methods in parasitic infections, and drug resistance is a challenging issue in long-term drug administration ( Ouellette, 2001 ; Montazeri et al, 2018 ; Ertabaklar et al, 2020 ). Previous studies indicated that stem cells played an important role in the treatment or control of schistosomiasis ( Miranda et al, 2020 ), malaria ( Souza et al, 2015 ), Chagas disease ( Silva et al, 2014 ), and hydatid cyst ( Abo-Aziza et al, 2019 ). Recently, Miranda et al (2020) reported that AD-MSCs could decrease liver damage in schistosomiasis through controlling the granulomatous reaction.…”

“…Previous studies indicated that stem cells played an important role in the treatment or control of schistosomiasis ( Miranda et al, 2020 ), malaria ( Souza et al, 2015 ), Chagas disease ( Silva et al, 2014 ), and hydatid cyst ( Abo-Aziza et al, 2019 ). Recently, Miranda et al (2020) reported that AD-MSCs could decrease liver damage in schistosomiasis through controlling the granulomatous reaction. On the other hand, stem cells have been introduced as a new therapeutic option for malaria ( Wang et al, 2015a ).…”