Effects of bone marrow mesenchymal stem cells transplantation at different time as well as the duration on hepatic fibrogenesis in rats*,☆

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Abstract

BACKGROUND:

Research demonstrated that hepatic fibrosis is suitable for the differentiation of bone marrow mesenchymal stem cells (MSCs), which suggests it is possible to treat hepatic fibrosis with MSCs transplantation.

OBJECTIVE:

To investigate the effects of MSCs transplantation at different times as well as the duration on hepatic fibrogenesis in rats.

DESIGN, TIME AND SETTING:

The in vivo cytology experiment was performed at the Fujian Medical University and Fujian Institute of Medical Sciences between November 2007 and August 2008.

MATERIALS:

Five male SD rats, with 5-6 weeks old were prepared for MSCs; 68 adult, male SD rats with clean grade were sacrificed at weeks 10 and 12 after model preparation. Rats killed at 10 weeks were divided into control and 6th weeks MSCs transplantation sub-groups, with 12 animals in each group. Rats killed at 12 weeks were divided into control, 6th weeks MSCs transplantation and 8th weeks MSCs transplantation sub-groups, with 16, 16 and 12 animals in each group.

METHODS:

Combined with stationary culture MSCs of male SD rats were isolated and purified by density gradient centrifugation. Totally 0.2 mL forth passage cells (5×106 mL), expanded by subculture, were respectively injected into the homogeneous female rats via the caudalis vena at weeks 6 and 8 after the hepatic fibrosis model induced by carbon tetrachloride (CCL4) in rats. In the control group, L-DMEM was injected with the same method.

MAIN OUTCOME MEASURES:

The Scheuer inflammation activity score and Schmid M fibrosis grading score.

RESULTS:

①Rats killed at 10 weeks: The Scheuer inflammation score of the 6th weeks MSCs transplantation group was obvious decreased than that of control group (t=−2.45, P=0.023), while there was no difference in inflammation activity grade was found (t=−0.60, P=0.554). ②Rats killed at 12 weeks: the Schmid M fibrosis score and Scheuer inflammation score were basically similar in control and 8th weeks MSCs transplantation groups (t=−0.21, P=0.84; t=−0.18, P=0.86), which was greater than the 6th weeks MSCs transplantation group (t=6.17, t=8.61, P < 0.01). ③Compared between rats killed at 10 weeks and killed at 12 weeks after model preparation, the fibrosis score and inflammation score was dramatically decreased in the 6th weeks MSCs transplantation group as the increasing of transplantation duration (t=−6.98, t=−9.78, P < 0.01).

CONCLUSION:

Early MSCs transplantation can alleviate inflammation reaction and improve fibrosis stage in transplanted rats induced by CCL4. The improve degree of inflammation reaction and fibrosis stage has a positive correlation with time.

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