Cord blood-derived mesenchymal stem cells with hepatogenic differentiation potential ameliorate chronic liver affection in experimental models.

BACKGROUND: The liver is one of the major target organs for which cell-based therapies are very promising. The limitations of various cellular therapies, including bone marrow (BM)-derived mesenchymal stem cells (MSCs), urges the exploration of stem cell sources more suitable for transplantation. Human umbilical cord blood (HUCB) can overcome these drawbacks with a favorable reparative outcome. OBJECTIVES: The aim of this study was to evaluate the therapeutic potential of MSCs in 2 groups of chronic liver injury experimental models. MATERIAL AND METHODS: Propagation and characterization of MSCs isolated from cord blood (CB) samples were performed and differentiation into osteogenic, adipogenic and hepatogenic lineages was induced. The 1st experimental model group (80 mice) included a negative control, a pathological control and 60 mice infected with Schistosoma mansoni (S. mansoni) and transplanted with MSCs. The 2nd experimental model group (30 hamsters) included 10 healthy hamsters serving as a negative control and 20 hamsters injected with repeated doses of carbon tetrachloride (CCl4) to induce liver fibrosis; 10 of them were treated with an intrahepatic (IH) injection of 3 × 106 MSCs and the other 10 were untreated pathological controls. Mice and hamsters were sacrificed 12 weeks post-transplantation and their liver sections were stained immunohistochemically for the detection of human hepatocyte-like cells. Moreover, the sections were examined for the levels of fibrosis. RESULTS: In both models, the transplantation of CB-derived MSCs (CB-MSCs) resulted in the engraftment of the fibrotic livers with newly formed hepatocytes, as evidenced by positive immunohistochemistry staining with human Hepatocyte Paraffin 1 (Hep Par 1), alpha-fenoprotein (AFP), cytokeratin 18 (CK18), cytokeratin 7 (CK7), and OV6 monoclonal antibody. The transplanted liver sections showed markedly reduced hepatic fibrosis with a significantly lower fibrotic index, as well as significantly improved liver functions compared to the pathological control (p < 0.001). CONCLUSIONS: This data provides hope that human CB-MSCs can be utilized as multipotent stem cells with unlimited potentiality in regenerative medicine and supports the concept of cellular therapy for the cure of hepatic fibrosis.

A Con A- purified hydatid glycoprotein fraction effectively diagnoses human hydatidosis.

Diagnosis and quantification of Echinococcus granulosus infection in man and animal hosts are centralized to feasible control. This study included 93 serum samples, 25 sure positive hydatid cases confirmed surgically, 7 suspected cases diagnosed by indirect haemagglutination IHA and 41 cases other parasitic infections (15 S. mansoni, 8 Fasciola, 7 Ascaris, 5 H. nana & 6 Ancylostoma) diagnosed by microscopic examination and were negative by ELISA and/or IHA for anti-hydatid antibody. Twenty negative serum samples served as healthy controls. Six types of hydatid fluid antigens (crude, host-free & Con-A purified) of human and camel origin were subjected to electrophoretic separation (SDS-PAGE) and immunoblotting (EITB). The anti-hydatid IgG was detected in sera of the different groups for evaluation of sensitivity, specificity and diagnostic efficacy of each type of antigens. Detection of circulating hydatid antigen (CAg) was performed using anti rabbit hyperimmune sera raised against Con-A purified either human or camel hydatid antigen. SDS-PAGE revealed several bands ranging from 55-185 kDa with 10 kDa band shared by all antigens. The specific bands revealed by EITB for Con-A purified camel and human antigens were at 80, 110 & 55, 110 kDa respectively. ELISA highest sensitivity (96.9%) was by using host-free Con-A purified glycoprotein fraction of human hydatid antigen. Highest specificity (98.4%) was recorded upon use of either Con-A purified camel or human antigen with 94.5% & 97.7% diagnostic efficacy respectively. Detection of circulating antigen by polyclonal antibodies against Con-A purified human hydatid antigen revealed 91.8% specificity.

Modified endocystectomy versus pericystectomy in echinococcus granulosus liver cysts: a randomized controlled study, and the role of specific anti-hydatid IgG4 in detection of early recurrence.

The evidence based data of hydatid liver disease indicate that the level of evidence was too low to help decide between radical or conservative surgeries (level IV evidence, grade C recommendation). So, there is a need for accurately designed randomized trials with precise goals to compare pericystectomy versus a specific modified endocystectomy technique for the treatment of hepatic hydatid cysts 8 cm or less in diameter in Egyptian patients, regarding the operative time, intra-operative blood loss, complications and long-term recurrence and to test the role of anti-hydatid IgG4 in diagnosis and detection of early recurrence. 60 patients with 131 liver cysts of E. granulosus fulfilling the study criteria were randomly divided to two groups. GI: 32 patients with 69 cysts treated by modified endocystectomy and GII: 28 patients with 62 cysts treated by closed total pericystectomy. GIa included 40 cysts >5 cm in diameter (mean 6.86, SD+/-0.809) & GIb 29 cysts < or = 5 cm in diameter (mean 4.17 SD+/-0.83). GIIa included 37 cysts >5 cm in diameter (mean 7.01 SD+/+0.79) & GIIb 25 cysts < or = 5 cm in diameter (mean 4.04 SD+/-0.93). Preoperative evaluation included history taking, clinical examination, blood tests, specific anti-hydatid IgG4, abdominal sonography and CT scan. The operative time for dealing with each cyst was in minutes. Operative blood loss and need for blood transfusion were estimated for each patient. Specific anti-hydatid IgG4 by ELISA was used to diagnose and to detect early recurrence. Patients were followed up clinically and by ultrasonography every 3 months and for anti-hydatid IgG4 every 6 months for 24-90 months. The mean maximum operative time was in GIIa followed by GIa, GIb, then GIIb. The operative time was significantly lower in GIIb than Ib and in GIa than IIa. Seven patients (GII) had blood transfusion. The intraoperative bleeding in GI was <500 ml/ patient, and 18 patients (GII) each bled >500 ml. No intraperitoneal seedling during the follow up. 5 of 55 patients (9%) were serologically suspected of relapse or incomplete cure. One (GII) showed early recurrence at 3 months. High IgG4 antibodies were detected in patients which decreased gradually after surgery and normal after 18 months post-operation.