Therapeutic Potential of Mesenchymal Stem Cells on Early and Late Experimental Hepatic Schistosomiasis Model

Abstract

Cell-based therapy is emerging as a promising therapeutic approach for a wide range of liver diseases. This study aimed to investigate the regenerative and antifibrotic therapeutic potential of bone marrow-derived mesenchymal stem cells (BM-MSCs) in an early and late experimental hepatic schistosomiasis model. BM-MSCs were isolated from 6-wk-old BALB/c donor male mice, then grown and propagated in culture until cell count was 5-8 × 10(6)/ml. MSCs were then separated and injected into Schistosoma mansoni -infected female BALB/c mice on their 6, 10, 14, and 18 wk post-infection. Mice were sacrificed on the fourth and eighth week after BM-MSCs transplantation in each group. Homing of BM-MSCs was confirmed by PCR detection of male Y-chromosome gene (sry) in the liver tissue of the recipient female mice. The regenerative and antifibrotic potential of BM-MSCs was assessed by histopathological examination, morphometric analysis, electron microscopy, and liver function tests. Schistosoma-infected mice, which were treated with BM-MSCs, showed a decrease in the granuloma size, percentage and density of the fibrotic area, formation of new hepatocytes, and improvement of the liver function tests. Immunohistochemical examination of alpha-smooth muscle actin revealed a significant decrease in the immunoreactive hepatic stellate cells in mice treated with MSCs. Early granulomas (acute infection) showed better response to MSC injection than did later granulomas (chronic infection). Dosing and timing of MSCs transplantation should undergo more investigations in long-term experiments before application to the clinical field. This study is the first to assess and compare the effect of MSCs treatment on early and late granulomas.

hUCMSC-extracellular vesicles downregulated hepatic stellate cell activation and reduced liver injury in S. japonicum-infected mice

“…Mesenchymal stem cells (MSCs) represent a promising therapeutic strategy for schistosome-induced liver injury [6][7][8][9][10], but this approach has been hindered by a limited understanding of the MSC-mediated control of liver injury in schistosomiasis. Extracellular vesicles (EVs) are small membrane vesicles released by almost all cell types, which contribute to donor cell-mediated biological effects [11,12].…”

Immunopathology in schistosomiasis is regulated by TLR2,4- and IFN-γ-activated MSC through modulating Th1/Th2 responses

“…Recently, based on widely anti-inflammatory effects, MSC has been employed to attenuate hepatic fibrosis induced by Schistosoma infection, and in parallel with the decreased hepatic stellate cell (HSC) activation and enhanced liver regeneration [5][6][7]. However, the effects of MSC on T cells, especially on Th1/Th2 modulation in this model, are still largely unknown.…”

Potential Therapeutic Effect of Allogenic Mesenchymal Stem Cells on Chronic Cerebral Murine Toxoplasmosis

“…It also enhances the cost benefit effectiveness and support the idea of xenogenic MSCs therapy trials in humans. This xenogenic transplantation was previously done with success by different authors who reported successful survival of xenogenic MSCs [17,31].…”

“…When cultures become confluent, the cultures were treated with 2 ml of 0.25 % trypsin/0.02 % EDTA for 2 min at 37 O C to detach cells from the flasks. Trypan blue was used to test the viability of cells, and then a hemocytometer was used to count the cells and adjusted to 10 6 cells /ml, then used immediately for animal treatment [17].…”