This study aimed to clarify the potentiality of bone marrow mesenchymal stem cells (BM-MSC) transplantation with albendazole (ABZ) on the modulation of immune responses against hydatid cyst antigens and the regeneration of injured livers in experimentally infected rats. Three different antigens of hydatid cyst fluid (HCF), hydatid cyst protoscolex (HCP) and hydatid cyst germinal layer (HCG) were isolated and their antigenic potencies were determined. The ultrasound, immunological and pathological criteria were investigated. Counting of 80% confluence BM-MSC was 4.68 × 104 cells/cm2 with 92.24% viability. Final population doublings score was 65.31 that indicated proliferation and self-renewability. Phenotyping of BM-MSC showed expression of CD73 and CD29 without exhibition of CD34 and CD14. Ultrasound examination showed multiple hydatid cysts in liver with low blood flow and spleenomegaly 8 weeks’ post infection. No significant differences were noted in cystic diameter in uni-cyst liver at 2nd and 4th weeks following ABZ treatment while it was significantly decreased (P < 0.05) following transplantation of BM-MSC + ABZ treatment comparing to experimentally infected untreated group. Igs and IgG responses to the three antigens were significantly elevated while elevation in IgM response was only to HCG (P < 0.05). ABZ treatment accompanied with significant decrease in Igs and IgG titers against HCF and HCG only at 4th week post treatment (P < 0.05). However, Igs titer against HCF, HCP and HCG was significantly decreased at the 4th week following transplantation of BM-MSC + ABZ. Interestingly, the combination of BM-MSC + ABZ treatment resulted in reduction of Igs response to HCP to normal level as that of healthy control. Experimental infection resulted in elevation of TNF-α and IL-6 (P < 0.05) while, IL-4 and IL-10 decreased (P < 0.01). After transplantation of BM-MSC + ABZ treatment, serum TNF-α and IL-6 concentrations were reduced (P < 0.05) at both the 2nd and 4th weeks. However, IL-4 and IL-10 concentrations were significantly elevated (P < 0.05) only at 4th week following transplantation of BM-MSC + ABZ treatment. In conclusion, BM-MSC transplantation following ABZ administration can regenerate injured liver tissue without complete disappearance of hydatid cyst. In addition, it can modulate host protective humeral and cell mediated immune responses against hydatid cyst antigens. Therefore, the current study encourages to move to the step of performing clinical trials in humans.
Background: In vitro impact of dihydrotestosterone (DHT) and 17-estradiol (E2) in osteogenic differentiation of castrated rat bone marrow mesenchymal stem cells (rBMMSC) still need to be clarified. Materials and Methods: The viability, proliferation and density of cultured rBMMSC isolated from sham operated (Sham) and castrated (Cast) male rats were evaluated. rBMMSC were cultured with osteogenic differentiating medium (ODM) in the presence of DHT (5,10 nM) and E2 (10,100 nM). Osteogenesis was evaluated by alizarin red staining and measurement of calcium deposition and bone alkaline phosphatase (BALP) activity. Results: Population doubling (PD) of rBMMSC isolated from Cast rats was significantly lower (P<0.05) compared to that isolated from Sham rats. rBMMSC from Cast rats showed low scattered calcified nodule after culturing in ODM and did not cause a significant increase in calcium deposition and B-ALP activity compared to rBMMSCs from Sham rats. Exposure of rBMMSC isolated from Cast rats to DHT (5 nM) or E2 (10 nM) in ODM showed medium scattered calcified nodules with significantly higher (P<0.05) calcium deposition and B-ALP activity. Moreover, exposure of rBMMSC to DHT (10 nM) or E2 (100 nM) showed high scattered calcified nodules with higher (P<0.01) calcium deposition and B-ALP activity Conclusion: These results indicated that the presence of testes might participate in controlling the in vitro proliferation and osteogenic differentiation capacity of rBMMSCs. DHT and E2 can enhance the osteogenic capacity of rBMMSCs in a dose-dependent manner. Based on these observations, optimum usage of DHT and E2 can overcome the limitations of MSCs and advance the therapeutic bone regeneration potential in the future.
Background and Aim: Toxocara vitulorum is a bovine intestinal nematode. Immune pictures following infection are conflicting and stopping anthelmintic albendazole treatment recording reversed liver abnormalities. The purpose of this work was to evaluate the therapeutic potential of bone marrow mesenchymal stem cells (BMMSCs) therapy, subsequent to albendazole administration in rats infected with T. vitulorum. Materials and Methods: The ultrasonographic and histopathological examinations as well as serum liver enzymes activity and the kinetics of recovery were investigated. The correlation of cell-mediated and humoral immune pictures was assessed by assaying immunoglobulins, splenocytes viability, phagocytic index, and Th1/Th2 cytokines. Results: The cultured BMMSCs counting were 4.21×104 cells/cm2 with 96.03% viability. Flow-cytometric analysis indicated positive CD90 (82%), CD105 (79%) and negative CD34 (0.37%), CD45 (0.42%), attesting to the suitability of the isolated BMMSCs for use in therapy. Transplantation of BMMSCs after albendazole administration significantly reduced the release of liver enzymes (p<0.05) indicating liver cellularity improvement. The ultrasonographic, macroscopic, and histopathological findings confirmed the biochemical results. Significant elevation in the levels of tumor necrosis factor (TNF)-α and interferon (INF)-γ with a decline in interleukin (IL)-4 was observed in the untreated model (p<0.05). However, albendazole treatment followed by BMMSCs therapy significantly lowered the release of TNF-α and INF-γ, associated with significant production of IL-4 and IL-10 (p<0.05). Conclusion: The final results indicated that the liver functions, histopathological findings, and immune parameters were aggravated after experimental T. vitulorum infection. Albendazole treatment followed by BMMSCs therapy was found to assist in regeneration of injured hepatic tissue. Besides, it appeared to modulate host defensive immune responses against T. vitulorum antigens. This work could define more clearly the events that manipulate the host immune, histopathological, and biochemical responses to minimize obstacles in using stem cell therapy in animal toxocariosis.
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