Matrix Metalloproteinases (MMPs) Activity in Cultured Canine Bone Marrow Stromal Cells (BMSCs)
Department of Veterinary Surgery, Faculty of Agriculture, Yamaguchi University, 1677-1 Yoshida, Yamaguchi 753-8515, Japan.Journal of Veterinary Medical Science (Impact Factor: 0.78). 12/2011; 74(5):633-6. DOI: 10.1292/jvms.11-0395
Autologous bone marrow stromal cells (BMSCs) infusion therapy improves the hepatic fibrosis. To investigate the mechanism of remission, we evaluated the matrix metalloproteinase (MMP)-2 and -9 activity in canine BMSCs and the effect of pro-inflammatory cytokines on their expression. The activity and the gene expression of MMPs were analyzed by gelatin zymography and quantitative RT-PCR, respectively. The specific gelatinase bands were indicative effect of MMP-2 and -9 in canine BMSCs. MMP-2 expression seemed to be increased by TNF-α and IL-1β while MMP-9 was enhanced by TNF-α and IL-6. These results suggested that remissive effect on liver fibrosis might be partly attributable to the MMP-2 and -9 activity in BMSCs under the inflammatory condition.
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ABSTRACT: Bone marrow cell infusion (BMI) has recently been suggested as an effective therapy for refractory liver disease; however, the efficiency of BMI using canine bone marrow cells (cBMCs) has not been reported. We evaluated the accumulation potential of cBMCs in a mouse model of acute liver failure. Acute hepatitis was induced by carbon tetrachloride (CCl(4)) treatment in NOD/SCID/γ(c)(null) (NOG) mice and wild-type (WT) C57BL mice and the characteristics of liver dysfunction and the degree of hepatic injury and regeneration was compared between the two mouse models. Next, female CCl(4)-treated NOG mice were xenotransplanted with male PKH26-labeled cBMCs and the potential of cBMCs to accumulate in injured liver tissue compartments was examined. Fluorescence microscopy was performed to histologically detect the infused cBMCs and DNA polymerase chain reaction was performed for detection of the male Y chromosome (SRY gene) in the recipient female NOG mice. The number of PKH26-positive cBMCs transplanted in the liver tissue gradually increased in the NOG mice. The infused cBMCs were located in the necrotic area of the liver at an early stage after transplantation, and most had accumulated a week after transplantation. However, the therapeutic efficacy of the xenotransplantation remained unclear because no significant differences were observed an extent of the liver injury and regeneration between the cBMCs transplanted and saline control mice. These results suggest that cBMCs will specifically accumulate in injured liver tissue and that BMC transplant may have the potential to repair liver deficiency.
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ABSTRACT: Bone marrow cells are capable of differentiation into liver cells. Therefore, transplantation of bone marrow cells has considerable potential as a future therapy for regeneration of damaged liver tissue. Autologous bone marrow infusion therapy has been applied to patients with liver cirrhosis, and improvement of liver function parameters has been demonstrated. In this review, we summarize clinical trials of regenerative therapy using bone marrow cells for advanced liver diseases including cirrhosis, as well as topics pertaining to basic in vitro or in vivo approaches in order to outline the essentials of this novel treatment modality.