Mesenchymal stem cells (MSCs) therapy show different levels of effectiveness in the context of different types of liver damage, suggesting that the microenvironment of the injured liver is a key ...determinant for effective stem cell therapy. The objective was to assess the modulatory effect of hepatic stem cell niche components on the transplanted MSCs during liver injury induced by carbon tetrachloride (CCl
). Superparamagnetic iron oxide (SPIO)-labeled human MSCs were injected intravenously into mice treated with CCl
and subjected to hepatic macrophage-depletion. Liver tissues were collected at different intervals post transplantation for subsequent histopathological, morphometric, immunohistochemical, gene expression and ultrastructural studies. The homing of the transplanted MSCs was evidenced by tracing them within the niche by iron staining and immunohistochemical studies. MSCs differentiated into hepatocyte-like cells and intimal smooth muscle cells as evidenced by their expression of human albumin and α-smooth muscle actin with a concomitant increase in the level of mouse hepatocyte growth factor. A post transplantation reduction in the liver fibro-inflammatory reaction was found and was promoted by liver macrophages depletion. Thus, it could be concluded from the present study that prior manipulation of the microenvironment is required to improve the outcome of the transplanted cells.
Objective
The present study was aimed to investigate and compare the kinetics of bone marrow‐derived hematopoietic stem cells (BMHSC) migration in the peripheral blood and liver in response to liver ...injury in patients with chronic liver disease (CLD).
Methods
In all, 45 CLD patients staged with Child–Pugh A, B and C and 15 healthy participants were evaluated for the concentration of circulating BMHSC by a flow cytometric analysis of CD133+/CD34+ cells. In addition, homing BMHSC and hepatic progenitors were assessed by the immunohistochemical detection of CD133+ and OV6+ cells in liver biopsy specimens from Child–Pugh A and B patients.
Results
No significant difference in the percentage of circulating CD133+/CD34+ cells was observed among all groups of patients. In liver tissues, OV6+ cells increased significantly in Child–Pugh B cases (P < 0.05), while CD133+ cells were distributed sparsely in the periportal region in Child–Pugh A and B patients. OV6+ cells were significantly correlated with CD34+ cells but not with CD133+ cells in Child–Pugh A and B patients (P < 0.01 and P < 0.05, respectively).
Conclusions
Various degrees of severity in CLD neither evoked the mobilization of BMHSC into the circulation nor triggered their homing into liver tissue, thus excluding extrahepatic stem cell‐mediated repair. The recovery process seems to be dependent on proliferating endogenous liver progenitors (OV6+ cells).
AIM:To introduce Granulocyte-colony stimulating factor (G-CSF) as a new therapeutic modality for schistosomiasis through stem cell mobilization,immunomodulation or fibrosis remodeling. METHODS:In ...this study,a 5 d course of human recombinant G-CSF (100 μg/kg sc) was applied to Schis-tosoma mansoni-infected mice at different stages of disease (5 d before infection as well as 3,5 and 7 wk post-infection). The animals were sacrificed at 10 d as well as 4,6 and 8 wk post infection. Mice were examined for:(1) Total leukocyte count which is an accepted surrogate marker for the stem cell mobilization into the circulation; (2) Egg count in intestine and liver tissue to assess the parasitic load; and (3) Histopathological changes in Hx/E and Masson trichrome stained sections as well as collagen content in Sirius redstained liver sections to determine the severity of liver fibrosis. RESULTS:Mice developed leukocytosis. The egg load and the number of granulomas were not affected by the G-CSF treatment but there was an obvious change in the composition of granulomas towards an increased cellularity. Moreover,fibrosis was significantly decreased in treated groups compared to untreated animals (collagen content either preinfection or at 3 and 5 wk post infection:5.8 ± 0.5,4.7 ± 0.5,4.0 ± 0.7 vs 8.2 ± 0.9; P ≤ 0.01). CONCLUSION:Although G-CSF did not cause direct elimination of the parasite,it enhanced granulomatous reaction and reduced the fibrosis. Further investigation of the underlying mechanisms of these two actions is warranted.
The discovery of the crude extract of Artemisia inculta (an Egyptian species of the Artemisia plant) for the therapy of schistosomiasis has evoked the study of its long-term toxicity produced by ...antischistosomal doses. Hence, an assessment of the noxious effects on bone marrow was attempted in this study. Transmission electron microscopy of the bone marrow was conducted on infected mice receiving a crude ethanolic extract from Artemisia inculta by newly designed dose regimens (500 or 800 mg/kg body weight in the 7th, 14th and 21st weeks post infection). This regimen was found to produce an efficient therapeutic effect in decreasing worm load and causing tegumental damage of juvenile and adult worms. The ultrastructural features of all cell lines in the bone marrow were comparable in both treated (500 and 800 mg/kg body weight dose levels) and untreated groups showing normal cellularity, maturation and morphology. This denotes that the drug is non-toxic to the hemopoietic tissue.
Electron microscopy has provided a direct and accurate evidence of the nontoxic property of the plant extract on bone marrow using therapeutic doses. However, this study should be extended to other vital organs such as the liver or brain to establish the safety of this drug.
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