Human umbilical cord blood mesenchymal stem cells as a potential therapy for schistosomal hepatic fibrosis: an experimental study

Abstract

The objective of our study was to assess the effect of human umbilical cord blood (HUCB) mesenchymal stem cells (MSCs) transplantation on schistosomal hepatic fibrosis in mice. The study animals were divided into three groups. Group I is a control group, where the mice were infected with Schistosoma mansoni cercariae and remained untreated. The mice of the other two groups were infected and treated with either praziquantel (Group II) or HUCB-MSCs (Group III). Liver function tests, as well as histopathological evaluation of liver fibrosis using hematoxylin and eosin and Masson's trichrome stains, were performed. Additionally, an immunohistochemical study was carried out using anti-glial fibrillary acidic protein (GFAP) in hepatic stellate cells. Compared to the control group, the treated (praziquantel and MSCs) groups showed a substantial improvement, with a significant difference regarding the histopathological evaluation of liver fibrosis in the MSCs-treated group. In conclusion, MSCs could be a promising and efficient cell therapy for liver fibrosis.

Keywords: Liver fibrosis; glial fibrillary acidic protein; mesenchymal stem cells; praziquantel; schistosomiasis.

Figure 1.

(a) Morphological characteristics of generated mesenchymal stem cells (MSC) using inverted light microscopy (x100). (b) High magnification illustrating the spindle-fibroblast-like shape of MSCs (x200).

Figure 2.

Flow cytometry dot plot showing (a) isotype negative control; (b) negative expression of CD34 and CD45 of MSCs after two weeks; (c) positive expression of CD90 of MSCs after two weeks; and (d) positive expression of CD105 of MSCs after two weeks.

Figure 3.

Hepatic biochemical parameter levels among the studied experimental animal groups: (a) serum ALT levels, (b) serum AST levels, and (c) serum albumin levels; showing significantly improved in treated group II and III compared to the infected non-treated control group I. ns: non-significant, * P values ˂ 0.05, ** P values ˂ 0.01, and *** P values ˂ 0.001.

Figure 4.

Histopathological changes of hematoxylin and eosin-stained liver of mice infected with Schistosoma mansoni twelve weeks post-infection (control: a & b; treated with praziquantel: c & d; and treated with mesenchymal stem cells: e & f) showing (a) multiple granulomas around Schistosoma mansoni ova and dilatation of portal vein branches with disruption of liver architecture (x100); (b) granuloma around Schistosoma mansoni ova with inflammatory cells mainly lymphocytes, plasma cells, and eosinophils with surrounding concentric fibrosis (x200); (c) & (e): reduction in the number of granulomas; and (d) & (f): decrease the inflammatory cellular infiltrate which is moderate in (d) (x200) and mild in (f) (x100) with insit higher magnification (x 200).

Figure 5.

Histopathological changes of Masson’s trichrome (MT)-stained livers of mice infected with Schistosoma mansoni twelve weeks post-infection showing (a) the control infected group with positive staining in the concentric fibrous layers surrounding the granuloma and in the wall of hepatic sinusoids (x200); (b) praziquantel-treated group with moderate positive staining (x200); and (c) mesenchymal stem cells-treated group with mild positive staining (x200). Note the reduction in the number and size of granulomas in both treated groups in comparison to the infected, untreated group.

Figure 6.

Hepatic granuloma diameter in the studied groups showing a reduction in the hepatic granuloma size in group II and the mesenchymal stem cell-treated group III than the control group I. ns: non-significant, * P values ˂ 0.05, ** P values ˂ 0.01, and *** P values ˂ 0.001.

Figure 7.

Immunohistochemical staining of glial fibrillary acidic protein (GFAP) in the livers of mice infected with Schistosoma mansoni twelve weeks post-infection showing (a) & (b) the infected, untreated group with intensely immunostained hepatic stellate cells (HSCs) present in the walls of sinuses (black arrow) as well as in the perivenular areas (x400) CV = central vein; (c) praziquantel-treated group with moderate GFAP expression in HSCs in the sinusoidal wall (x200); (d) mesenchymal stem cells-treated group with mild GFAP expression (x400) G = granuloma; and (e) The percentage HSCs positive for GFAP expression in the liver of the studied experimental animal groups. ns: non-significant, * P values ˂ 0.05, ** P values ˂ 0.01, and *** P values ˂ 0.001.