Bone marrow cells reduce fibrogenesis and enhance regeneration in fibrotic rat liver.
BACKGROUND
This study aimed at investigating the cellular and molecular impacts of bone marrow-derived mononuclear cells (BMCs) on regeneration of fibrotic liver in rats.


METHODS
Thirty male adult Fisher rats were randomized into three groups: group 1 (normal controls, n = 10); group 2 (carbon tetrachloride-induced liver fibrosis, n = 10), and group 3 (liver fibrosis with portal venous infusion of autologous BMCs, 1 × 10(6), n = 10). After 7-d culturing, BMCs were characterized by flow cytometry. Groups 2 and 3 received BMC aspiration through bilateral femurs 5 d before hepatectomy. All animals received 70% hepatectomy, whereas only group 3 received a bolus of intra-portal BMC infusion 48 h after hepatectomy. Liver-to-body weight ratio, degree of fibrosis (Masson trichrome staining), oxidative stress, peroxisome proliferator activated receptor-γ coactivator-1α (PGC-1α), collagen I, tumor necrosis factor-α (TNF-α), and transforming growth factor- β (TGF-β) expressions were analyzed 14 d after hepatectomy. Immunohistochemical staining for albumin, α-smooth muscle actin, and CD31 was performed for tracing cellular differentiation.


RESULTS
Cellular phenotypes typical of hepatocyte, hepatic stellate cell (HSC), and endothelial cell were identified in the engrafted BMCs. Liver-to-body weight ratio was enhanced with PGC-1α significantly preserved, whereas oxidative index, collagen I, α-SMA, TNF-α, and TGF-β expressions were all decreased in group 3 compared with group 2 (all P < 0.05).


CONCLUSIONS
This study demonstrated a positive impact of intra-portal BMC infusion in enhancing regeneration and reducing fibrosis of the regenerating fibrotic liver in rats through suppressing HSC activation and inflammatory cytokine expressions, preserving mitochondrial function and reducing oxidative stress.
Sun
Cheuk-Kwan
CK
Division of General Surgery, Chang Gung Memorial Hospital, Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung Hsien, Taiwan, ROC.
Chen
Chih-Hung
CH
Kao
Ying-Hsien
YH
Yuen
Chun-Man
CM
Sheu
Jiunn-Jye
JJ
Lee
Fan-Yen
FY
Chen
Yen-Ta
YT
Kung
Chia-Te
CT
Yip
Hon-Kan
HK
D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology / Q000502:physiology*; D002251:Carbon Tetrachloride / Q000009:adverse effects; D064987:Cell- and Tissue-Based Therapy / Q000379:methods*; D002478:Cells, Cultured; D024042:Collagen Type I / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D022781:Hepatocytes / Q000473:pathology; D008103:Liver Cirrhosis / Q000139:chemically induced / Q000503:physiopathology* / Q000517:prevention & control*; D008115:Liver Regeneration / Q000502:physiology*; D008297:Male; D008930:Mitochondria, Liver / Q000502:physiology; D018384:Oxidative Stress / Q000502:physiology; D051381:Rats; D011916:Rats, Inbred F344; D016896:Treatment Outcome
D024042:Collagen Type I; D016207:Cytokines; D002251:Carbon Tetrachloride