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Bone Marrow Cells Reduce Collagen Deposition in the Rat Model of Common Bile Duct Ligation

Guilherme Baldo, Nelson Alexandre Kretzmann, Juliana Tieppo, Gustavo Pereira Filho, Carolina Uribe Cruz, Luise Meurer, Themis Reverbel da Silveira, Jorge Luis dos Santos, Cláudio Augusto Marroni, Norma Possa Marroni, Roberto Giugliani and Ursula Matte

Background and Aim: Transplantation of bone marrow cells (BMC) was shown to improve liver function in animal models of cirrhosis. In this work we evaluated the effects of mononuclear BMC transplantation in rats submitted to bile duct ligation (BDL), a model of cholestatic liver disease. Methods: BDL was performed on Wistar rats, and two weeks later animals underwent a liver biopsy. At the same time, BMC group was injected with 1x106 mononuclear BMC and compared to untreated (BDL) and a fake-surgery (Sham) group. Animals were sacrificed two weeks later. Alkaline Phosphatase (ALP) and collagen deposition quantified by Sirius red staining were analyzed at both time points. MMP-9 expression assessed by immunohistochemistry and liver oxidative stress parameters (TBARS, SOD and catalase activity) was performed at four weeks. The effect of BMC-conditioned medium upon activated hepatic stellate cells was tested in vitro by MTT using GRX cells. Results: Treated animals showed a 25% decrease in ALP levels at four weeks. Collagen deposition in untreated group at 4 weeks had values 2-fold higher, compared to those found in the biopsy. In contrast, BMC-treated rats barely increased collagen deposition after treatment (p< 0.01). No difference was observed in MMP-9 expression nor in oxidative stress parameters. BMC-conditioned medium was able to induce cell death on GRX cells in vitro. Conclusions: A decrease in collagen deposition and a reduction in ALP levels suggest a better outcome in the treated group. The effect of BMC conditioned medium in vitro suggests a possible mechanism for the reduction of fibrosis observed in vivo.