Hematopoietic stem cell mobilization into the peripheral circulation in patients with chronic liver diseases.

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).

Does granulocyte-colony stimulating factor administration induce damage or repair response in schistosomiasis?

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 Schistosoma 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 red-stained 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.

Immunological and parasitological parameters after treatment with dexamethasone in murine Schistosoma mansoni

This work aimed to evaluate the effect of diphenyl dimethyl bicarboxylate (DDB) and dexamethasone alone and in combination with praziquantel on various parasitological, immunological and pathological parameters reflecting disease severity and morbidity in murine schistosomiasis. DDB and dexamethasone had no effect on worm burden but altered tissue egg distribution. This indicates that, under the schedule used, neither drug interfered with the development of adult worms or oviposition, but both can modulate liver pathology. Dexamethasone resulted in a greater reduction in granuloma size than did DDB. Dexamethasone-treated mice also showed lower levels of serum gamma interferon (IFN-γ), interleukin-12 (IL-12) and IL-4, together with higher IL-10 levels, than infected untreated control animals. These data suggest that dexamethasone is a convenient and promising coadjuvant agent that results in decreased morbidity in murine schistosomiasis.