Construction of liver tissue in vivo with preparative partial hepatic irradiation and growth stimulus: Investigations of less invasive techniques and progenitor cells

Kensuke Miyazaki, Kosho Yamanouchi, Yusuke Sakai, Izumi Yamaguchi, Mitsuhisa Takatsuki, Tamotsu Kuroki, Chandan Guha, Susumu Eguchi

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Background: The selective proliferation of transplanted hepatocytes with a growth stimulus, such as partial hepatectomy or hepatocyte growth factor, concomitant with hepatic irradiation (HIR), which can suppress proliferation of host hepatocytes, has been reported. We have conducted experiments that focused on less invasive and clinically applicable techniques and progenitor cells. Materials and methods: First, dipeptidyl-peptidase IV-F344 or jaundiced Gunn rats underwent partial HIR (only 30% of whole liver) and portal vein branch ligation (PVBL) of one lobe, followed by intrasplenic hepatocyte transplantation at 1 × 107. Second, after partial HIR and PVBL, two types of progenitor cells were transplanted (i.e., small hepatocytes (SHs) or adipose-derived mesenchymal stem cells. Results: Sixteen weeks after transplantation, the donor cells constituted < 70% of the hepatocytes of the irradiated lobe, showing connexin 32, phosphoenolpyruvate carboxykinase-1, and glycogen storage. Moreover, the serum bilirubin level had decreased significantly in the jaundiced Gunn rats and remained at this level throughout the 24 wk experimental period. The SHs grew more quickly than the hepatocytes. After 8 wk, around 40% of the host hepatocytes had been replaced by transplanted SHs. Although the donor adipose-derived mesenchymal cells were engrafted after 8 wk, their proliferation was not observed. Conclusions: HIR, combined with PVBL, can be given to a selective liver lobe and is a lessinvasive but effective method for proliferation of transplanted hepatocytes. Even a smaller number of SHs can construct liver tissue with their prevailing proliferative ability.

Original languageEnglish (US)
Pages (from-to)889-895
Number of pages7
JournalJournal of Surgical Research
Volume185
Issue number2
DOIs
StatePublished - Dec 2013

Fingerprint

Hepatocytes
Stem Cells
Liver
Growth
Portal Vein
Gunn Rats
Ligation
Jaundice
Dipeptidyl Peptidase 4
Phosphoenolpyruvate
Hepatic Veins
Hepatocyte Growth Factor
Cell Transplantation
Hepatectomy
Mesenchymal Stromal Cells
Glycogen
Bilirubin
Transplantation
Serum

Keywords

  • Adipose-derived mesenchymal stem
  • Cell
  • Hepatic irradiation
  • Hepatocyte transplantation
  • Portal vein branch ligation
  • Small hepatocyte

ASJC Scopus subject areas

  • Surgery
  • Medicine(all)

Cite this

Construction of liver tissue in vivo with preparative partial hepatic irradiation and growth stimulus : Investigations of less invasive techniques and progenitor cells. / Miyazaki, Kensuke; Yamanouchi, Kosho; Sakai, Yusuke; Yamaguchi, Izumi; Takatsuki, Mitsuhisa; Kuroki, Tamotsu; Guha, Chandan; Eguchi, Susumu.

In: Journal of Surgical Research, Vol. 185, No. 2, 12.2013, p. 889-895.

Research output: Contribution to journalArticle

Miyazaki, Kensuke ; Yamanouchi, Kosho ; Sakai, Yusuke ; Yamaguchi, Izumi ; Takatsuki, Mitsuhisa ; Kuroki, Tamotsu ; Guha, Chandan ; Eguchi, Susumu. / Construction of liver tissue in vivo with preparative partial hepatic irradiation and growth stimulus : Investigations of less invasive techniques and progenitor cells. In: Journal of Surgical Research. 2013 ; Vol. 185, No. 2. pp. 889-895.
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abstract = "Background: The selective proliferation of transplanted hepatocytes with a growth stimulus, such as partial hepatectomy or hepatocyte growth factor, concomitant with hepatic irradiation (HIR), which can suppress proliferation of host hepatocytes, has been reported. We have conducted experiments that focused on less invasive and clinically applicable techniques and progenitor cells. Materials and methods: First, dipeptidyl-peptidase IV-F344 or jaundiced Gunn rats underwent partial HIR (only 30{\%} of whole liver) and portal vein branch ligation (PVBL) of one lobe, followed by intrasplenic hepatocyte transplantation at 1 × 107. Second, after partial HIR and PVBL, two types of progenitor cells were transplanted (i.e., small hepatocytes (SHs) or adipose-derived mesenchymal stem cells. Results: Sixteen weeks after transplantation, the donor cells constituted < 70{\%} of the hepatocytes of the irradiated lobe, showing connexin 32, phosphoenolpyruvate carboxykinase-1, and glycogen storage. Moreover, the serum bilirubin level had decreased significantly in the jaundiced Gunn rats and remained at this level throughout the 24 wk experimental period. The SHs grew more quickly than the hepatocytes. After 8 wk, around 40{\%} of the host hepatocytes had been replaced by transplanted SHs. Although the donor adipose-derived mesenchymal cells were engrafted after 8 wk, their proliferation was not observed. Conclusions: HIR, combined with PVBL, can be given to a selective liver lobe and is a lessinvasive but effective method for proliferation of transplanted hepatocytes. Even a smaller number of SHs can construct liver tissue with their prevailing proliferative ability.",
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T2 - Investigations of less invasive techniques and progenitor cells

AU - Miyazaki, Kensuke

AU - Yamanouchi, Kosho

AU - Sakai, Yusuke

AU - Yamaguchi, Izumi

AU - Takatsuki, Mitsuhisa

AU - Kuroki, Tamotsu

AU - Guha, Chandan

AU - Eguchi, Susumu

PY - 2013/12

Y1 - 2013/12

N2 - Background: The selective proliferation of transplanted hepatocytes with a growth stimulus, such as partial hepatectomy or hepatocyte growth factor, concomitant with hepatic irradiation (HIR), which can suppress proliferation of host hepatocytes, has been reported. We have conducted experiments that focused on less invasive and clinically applicable techniques and progenitor cells. Materials and methods: First, dipeptidyl-peptidase IV-F344 or jaundiced Gunn rats underwent partial HIR (only 30% of whole liver) and portal vein branch ligation (PVBL) of one lobe, followed by intrasplenic hepatocyte transplantation at 1 × 107. Second, after partial HIR and PVBL, two types of progenitor cells were transplanted (i.e., small hepatocytes (SHs) or adipose-derived mesenchymal stem cells. Results: Sixteen weeks after transplantation, the donor cells constituted < 70% of the hepatocytes of the irradiated lobe, showing connexin 32, phosphoenolpyruvate carboxykinase-1, and glycogen storage. Moreover, the serum bilirubin level had decreased significantly in the jaundiced Gunn rats and remained at this level throughout the 24 wk experimental period. The SHs grew more quickly than the hepatocytes. After 8 wk, around 40% of the host hepatocytes had been replaced by transplanted SHs. Although the donor adipose-derived mesenchymal cells were engrafted after 8 wk, their proliferation was not observed. Conclusions: HIR, combined with PVBL, can be given to a selective liver lobe and is a lessinvasive but effective method for proliferation of transplanted hepatocytes. Even a smaller number of SHs can construct liver tissue with their prevailing proliferative ability.

AB - Background: The selective proliferation of transplanted hepatocytes with a growth stimulus, such as partial hepatectomy or hepatocyte growth factor, concomitant with hepatic irradiation (HIR), which can suppress proliferation of host hepatocytes, has been reported. We have conducted experiments that focused on less invasive and clinically applicable techniques and progenitor cells. Materials and methods: First, dipeptidyl-peptidase IV-F344 or jaundiced Gunn rats underwent partial HIR (only 30% of whole liver) and portal vein branch ligation (PVBL) of one lobe, followed by intrasplenic hepatocyte transplantation at 1 × 107. Second, after partial HIR and PVBL, two types of progenitor cells were transplanted (i.e., small hepatocytes (SHs) or adipose-derived mesenchymal stem cells. Results: Sixteen weeks after transplantation, the donor cells constituted < 70% of the hepatocytes of the irradiated lobe, showing connexin 32, phosphoenolpyruvate carboxykinase-1, and glycogen storage. Moreover, the serum bilirubin level had decreased significantly in the jaundiced Gunn rats and remained at this level throughout the 24 wk experimental period. The SHs grew more quickly than the hepatocytes. After 8 wk, around 40% of the host hepatocytes had been replaced by transplanted SHs. Although the donor adipose-derived mesenchymal cells were engrafted after 8 wk, their proliferation was not observed. Conclusions: HIR, combined with PVBL, can be given to a selective liver lobe and is a lessinvasive but effective method for proliferation of transplanted hepatocytes. Even a smaller number of SHs can construct liver tissue with their prevailing proliferative ability.

KW - Adipose-derived mesenchymal stem

KW - Cell

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KW - Small hepatocyte

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