[Effect of interleukin 10 gene-modified bone marrow-derived liver stem cells transplantation on hepatic inflammatory response and liver regeneration in hepatic fibrosis rats].
OBJECTIVE
To explore effect of interleukin 10 (IL-10) gene-modified bone marrow-derived liver stem cells (BDLSCs) transplantation on hepatic inflammatory response and liver regeneration in rats with liver fibrosis.


METHODS
50 female Wistar rats were randomly divided into 4 groups: (1) control group: 10 rats were subcutaneously injected with olive oil for 8 weeks; (2) fibrosis groups: 16 rats were subcutaneously injected with carbon tetrachloride (CCl4) for 8 weeks to induce liver fibrosis; (3) BDLSC group: 12 rats were subcutaneously injected with CCl4 for 8 weeks, and were transplanted with 2 x 10(5) BDLSC at week 4; (4) BDLSC/IL-10 group: 12 rats were subcutaneously injected with CCl4 for 8 weeks, and were transplanted with 2 x 10(5) IL-10 gene-modified BDLSC at week 4. IL-10 and tumor necrosis factor alpha (TNFa) in liver tissues were detected by ELISA. HE stained liver tissues were observed under light microscope. The expression of hepatocyte growth factor (HGF) was quantified by real-time RT-PCR, and the expression of proliferating cell nuclear antigen (PCNA) was determined by immunohistochemistry.


RESULTS
The ratio of IL-10/TNFa in fibrosis group (0.05+/-0.01) was lower than that in control group (0.26+/-0.04) (P < 0.01). Transplantation of untreated BDLSCs did not improve the ratio (P > 0.05), however, transplantation of IL-10 modified BDLSCs improved the ratio significantly (P < 0.01). Severe inflammatory response and fibrosis were observed in fibrosis group. Inflammatory response was alleviated to some extent in the BDLSC group, and the histopathology of BDLSC/IL-10 group was not significantly different from that of the control group. Compared to the control group, the expression of HGF mRNA and PCNA protein was increased in the fibrosis group (P < 0.01). The expression of HGF and PCNA was further increased by BDLSCs or IL-10 modified BDLSCs transplantation. Compared to BDLSCs, IL-10 gene-modified BDLSCs were more potent to induce the expression of HGF and PCNA.


CONCLUSIONS
Transplantation of IL-10 gene-modified BDLSCs can alleviate hepatic inflammatory response and promote liver regeneration in hepatic fibrosis rats.
Lan
Ling
L
Digestive Department, the People's Hospital of Henan Province, Zhengzhou 450003, China.
Chen
Yuan-wen
YW
Sun
Chao
C
Liu
Bo-wei
BW
Sun
Qiao-ling
QL
Li
Ding-guo
DG
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology*; D049109:Cell Proliferation; D004195:Disease Models, Animal; D005260:Female; D015316:Genetic Therapy / Q000379:methods; D017228:Hepatocyte Growth Factor / Q000235:genetics / Q000378:metabolism; D007150:Immunohistochemistry; D016753:Interleukin-10 / Q000235:genetics*; D008099:Liver / Q000378:metabolism* / Q000473:pathology; D008103:Liver Cirrhosis / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D008115:Liver Regeneration; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D033581:Stem Cell Transplantation / Q000379:methods; D014161:Transduction, Genetic; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D017228:Hepatocyte Growth Factor