Contribution Of Bone Marrow Cells Transplantation In The Treatment Of Acute Liver Injury

ObjectiveTo investigate the contribution of bone marrow cells transplantation in the treatment of acute liver injury induced by carbon tetrachloride,and the differentiation of transplanted bone marrow cells into hepatocytes in vivo. MethodsAfter acute liver injury induced by carbon tetrachloride(CCL4)and transplantation with bone marrow cells within 24 hours,murine serum were collected and tested for AST and ALT,as well as liver tissue calculated for the necrosis area at different stages after transplantation.Liver tissue of CCL4-treated mice who received green fluorescence protein(GFP)transgenic mouse bone marrow cells transplantation were detected for bone marrow-derived hepatocytes with double immunofluorescence staining at different days after transplantation.Hepatocytes were isolated from receptor's liver and cultured in vitro to study the characteristic.Results(1)The significantly decreased levels of serum hepatic parameters ALT in CCL4-treated mice received bone marrow transplantation compared with non-transplantation group at 96hours,7days,10days after transplantation Was observed,while the significantly decreased levels of the serum hepatic parameters AST at 72hours,96hours,7days,10days after transplantation and the significant decline of liver necrotic area at 72hours and 96hours after transplantation was testified.(2)Hematopoietic stem cells derived from transplantated bone marrow cells always exist in liver sinusoid during 8 weeks follow-up.Immature hepatocytes expressing AFP differentiated from transplantated bone marrow cells can be identified since 1 week after transplantation,while mature hepatocytes differentiated from transplantated bone marrow cells and no-expressing CD34 can be observed until 4 weeks after transplantation.(3)Significant increase of immature hepatocytes rather than mature hepatocytes was identified when mouse pretreated with 2-AAF before bone marrow transplantation.(4)No clone result from bone marrow derived-hepatocytes with autofluorescence can be observed during 2 weeks follow-ups after isolated from liver.Bone marrow derived-hepatocytes,which average diameter after attached was 24.9±9.2um,only CO-expressed GFP and AFP rather than GFP with Desmin, CD34,CD16.Conclusion(1)Bone marrow transplantation contributes the recovery of serum hepatic parameters and liver necrotic area in CCIA-treated mice,which is one of the potential therapy for acute liver injury or failure.(2)Bone marrow transplantation contributes to liver repopulation by differentiation into immature and mature hepatocytes after transplantated into CCL4-treated mouse.(3)Bone marrow derived-hepatocytes probably have no the property of liver progenitor cells.