Transplantation of Flk-1+ human bone marrow-derived mesenchymal stem cells promotes behavioral recovery and anti-inflammatory and angiogenesis effects in an intracerebral hemorrhage rat model.

Mesenchymal stem cells (MSCs) have been successfully used for the treatment of experimental intracerebral hemorrhage (ICH). However, the neuroprotective mechanisms through which MSCs improve neurological functional recovery are not fully understood. In the present study, we tested the hypothesis that treatment with MSCs inhibits inflammation after ICH and reduces subsequent brain injury. Adult rats subjected to stereotaxic injection of collagenase VII were transplanted with a subpopulation of human bone marrow-derived MSCs (hBMSCs), termed fetal liver kinase (Flk)-1(+) hBMSCs, or saline into the ipsilateral brain parenchyma 1 day after ICH. Significant recovery of behavior was noted in the Flk-1(+) hBMSC-treated rats beginning 3 days after ICH compared with the control group. Brain water content was significantly decreased in the ipsilateral hemispheres of the Flk-1(+) hBMSC-treated rats when compared with the controls 3 days after ICH. The relative hemorrhage volume was reduced 55 days after Flk-1(+) hBMSC treatment. However, this change was not statistically significant. Flk-1(+) hBMSCs significantly inhibited the proliferation of rat peripheral blood mononuclear cells (rPBMCs) induced in a mixed lymphocyte reaction. Consistently, we found a significant anti-inflammatory effect of Flk-1(+) hBMSCs on the ICH brain, including a decrease in neutrophil infiltration and microglial activation in the peri-ICH area, and downregulation of inflammatory mediators, such as interleukin (IL)-1ß, IL-2, IL-4, IL-6, and tumor necrosis factor (TNF)-α. In addition, Flk-1+ hBMSC treatment significantly increased vascular density in the peri-ICH area, and transplanted Flk-1(+) hBMSCs were found to be incorporated into the cerebral vasculature 55 days after transplantation. Overall, these data suggest an essential role for Flk-1(+) hBMSCs in reducing inflammatory infiltration, promoting angiogenesis, and improving functional recovery after ICH in rats.

[Occult hepatitis B virus infection in chronic viral hepatitis patients with non-A to E hepatitis virus infection].

OBJECTIVE: To observe the status of occult hepatitis B virus infection in chronic viral hepatitis patients with non-A to E hepatitis virus infection and explore the diagnostic value of fluorescence quantitative polymerase chain reaction (FQ-PCR) technique for occult hepatitis B virus infection. METHODS: The amount of HBV-DNA in serum and liver tissue from 57 patients with non-A to E hepatitis virus infection who were diagnosed as chronic viral hepatitis by Menghini method liver biopsy were detected by using FQ-PCR technique, then the relation between the viral load of HBV DNA in liver tissue and hepatic inflammatory activity were analyzed. RESULTS: Thirteen (22.81%), 22 (38.60%) patients were positive for HBV DNA in serum and liver tissue, respectively. The positive rate and the level of HBV DNA quantity in liver tissue were significantly higher than those in serum; HBV DNA was found positive in both serum and liver tissue in 13 cases, negative in both serum and liver tissue in 35, positive in liver tissue but negative in serum in 9, and in none of the cases HBV DNA was positive in serum but negative in liver tissue (P < 0.01). The logarithmic value of HBV DNA from 13 patients in liver tissue and in serum was respectively: (6.62 +/- 1.21) copies/g vs.(4.03 +/- 1.06) copies/ml, P < 0.01. The hepatic lesions of all HBV DNA positive patients were active pathologic changes, but the level of HBV DNA in liver tissue was not significantly correlated with the grade of hepatic inflammation activity (P > 0.05). CONCLUSION: Occult HBV infection is the etiology of part of the chronic viral hepatitis patients with non-A-E hepatitis virus infection. Missed diagnosis will occur if diagnosis of hepatitis B is only based on detection of serum HBV markers. It is useful for improvement of the diagnostic level of HBV infection via detection of HBV DNA quantitatively in serum especially in liver tissue of chronic viral hepatitis patients with non-A-E hepatitis virus infection by using FQ-PCR technique. The chronic viral hepatitis patients with occult HBV infection should be also given effective anti-viral therapy.