Wharton's jelly-derived mesenchymal stem cells combined with praziquantel as a potential therapy for Schistosoma mansoni-induced liver fibrosis.

Olfat A Hammam,Sanaa A Kenawy,Nagwa Elkhafif,Aiman S El-Khatib,Mohamed M Elmazar,Yasmeen M Attia,Mohamed T Mansour,Rania M Abdelsalam

doi:10.1038/srep21005

Abstract

Liver fibrosis is one of the most serious consequences of S. mansoni infection. The aim of the present study was to investigate the potential anti-fibrotic effect of human Wharton’s jelly-derived mesenchymal stem cells (WJMSCs) combined with praziquantel (PZQ) in S. mansoni-infected mice. S. mansoni-infected mice received early (8th week post infection) and late (16th week post infection) treatment with WJMSCs, alone and combined with oral PZQ. At the 10th month post infection, livers were collected for subsequent flow cytometric, histopathological, morphometric, immunohistochemical, gene expression, and gelatin zymographic studies. After transplantation, WJMSCs differentiated into functioning liver-like cells as evidenced by their ability to express human hepatocyte-specific markers. Regression of S. mansoni-induced liver fibrosis was also observed in transplanted groups, as evidenced by histopathological, morphometric, and gelatin zymographic results besides decreased expression of three essential contributors to liver fibrosis in this particular model; alpha smooth muscle actin, collagen-I, and interleukin-13. PZQ additionally enhanced the beneficial effects observed in WJMSCs-treated groups. Our results suggest that combining WJMSCs to PZQ caused better enhancement in S. mansoni-induced liver fibrosis, compared to using each alone.

Highlights

IntroductionWharton’s jelly-derived MSCs (WJMSCs) may be superior to BMSCs for being more primitive representing an early-stage mesenchymal-like stem cells and more collected without ethical restrictions[5]
We provided data suggesting the differentiation of Wharton’s jelly-derived MSCs (WJMSCs) transplanted in S. mansoni-infected mice into functioning liver-like cells leading to regression of fibrosis-related markers, especially when PZQ was given in combination
The degree of fibrosis resolution was greatly dependant on the time at which treatment with WJMSCs was initiated

Summary

Introduction

Wharton’s jelly-derived MSCs (WJMSCs) may be superior to BMSCs for being more primitive representing an early-stage mesenchymal-like stem cells and more collected without ethical restrictions[5]. Previous studies have shown that WJMSCs minimally express major histocompatability complex class II antigens and costimulatory molecules suggesting that they are a favorable cell source for transplantation, without the need for immunosuppression[7]. We hereby investigated the therapeutic potential of combining either early or late WJMSCs treatment to PZQ on both acute and chronic stages of Schistosoma mansoni-induced liver fibrosis in mice, respectively. Our results have suggested the capability of WJMSCs to differentiate into functioning liver-like cells. Using PZQ in combination with WJMSCs caused better enhancement in the S. mansoni-induced liver fibrosis, presumably by improving the microenvironment at sites of engraftment reaching for a better interaction between stem cells and the damaged liver tissue

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