Bone marrow cells enhance liver regeneration after massive hepatectomy in mice.
BACKGROUND
Recent evidence indicates that transplanted autologous bone marrow cells (BMCs) can be converted into functional liver cells. BMC therapy can improve hepatic function and increase the potential for liver regeneration in patients with serious liver damage. We investigated whether BMC therapy influenced liver regeneration after massive hepatectomy in mice.


METHODS
Male C57/BL6 mice underwent 70 % hepatectomy, followed by injection of BMCs via the portal vein (PV group), BMCs via the tail vein (IV group), or saline via the portal vein (control group). Analysis of serum enzyme levels and liver histology was performed on postoperative days (POD) 1, 3, and 5.


RESULTS
Compared with the control group, the rate of liver regeneration on POD 3 and 5 was significantly higher in the PV group, but not in the IV group. Examination of the mitotic index and Ki-67 labeling index revealed that the increased liver regeneration resulted from stimulation of DNA synthesis. On POD 3, the serum levels of interleukin (IL)-6 and hepatocyte growth factor (HGF) were significantly higher and the expression of IL-6 and HGF mRNA in the remnant liver tended to be higher in the PV group than in the control group. Histological examination showed BMCs in the liver of the PV group, as well as conversion of BMCs into liver cells.


CONCLUSIONS
Our findings indicate that the injection of BMCs via the portal vein, but not the injection of BMCs via the tail, enhances liver regeneration after massive hepatectomy in mice.
Department of Surgery, Hirakata Hospital, Kansai Medical University, 2-3-1 Shinmachi, Hirakata, Osaka, 573-1191, Japan, kaibori@hirakata.kmu.ac.jp.
Masaki
M
Kaibori
Yasushi
Y
Adachi
Tomohiko
T
Shimo
Morihiko
M
Ishizaki
Kosuke
K
Matsui
Yoshito
Y
Tanaka
Masaharu
M
Ohishi
Yoshiro
Y
Araki
Katsuji
K
Tokuhara
Tadayoshi
T
Okumura
Mikio
M
Nishizawa
A-Hon
AH
Kwon
D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D016026:Bone Marrow Transplantation / Q000379:methods*; D006498:Hepatectomy; D017228:Hepatocyte Growth Factor / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008099:Liver / Q000378:metabolism / Q000473:pathology / Q000601:surgery; D008115:Liver Regeneration; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D011182:Postoperative Care / Q000379:methods*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014182:Transplantation, Autologous; D016896:Treatment Outcome
D015415:Biomarkers; C553307:HGF protein, mouse; D015850:Interleukin-6; D017228:Hepatocyte Growth Factor