Scaffolds containing growth factors and extracellular matrix induce hepatocyte proliferation and cell migration in normal and regenerating rat liver.
OBJECTIVE
Intrahepatic drug delivery from implantable scaffolds is being developed as a strategy to modulate growth and enhance regeneration at the time of liver resection. In this study we examine the effects of scaffolds containing hepatocyte growth factor, epidermal growth factor, fibroblast growth factor 1, fibroblast growth factor 2, and liver-derived extracellular matrix (L-ECM) when implanted into normal and partially hepatectomized rat livers.


METHODS
Scaffolds loaded with combinations of growth factors and L-ECM were implanted into normal livers (controls=L-ECM, polymer or sham) and livers following partial hepatectomy (controls=partial hepatectomy or sham). The primary end points were hepatocyte DNA synthesis and liver tissue penetration into scaffolds. Secondary end points included non-parenchymal cell DNA synthesis, liver weight analysis, liver function, and histological characterisation of the peri-implant parenchyma.


RESULTS
Four days after implantation in normal livers, there was significantly more hepatocyte proliferation around growth factor scaffolds than controls. Seven days after implantation, there was significantly more tissue penetration into growth factor scaffolds than control scaffolds. ED-1 and desmin positive cells were present in the pores of scaffolds. Two days after partial hepatectomy, there was significantly more hepatocyte proliferation around scaffold implanted livers than after partial hepatectomy alone.


CONCLUSIONS
Growth factors and L-ECM accelerated non-parenchymal cell migration into scaffolds and increased hepatocyte and non-parenchymal cell proliferation around them. These results demonstrate the potential for intrahepatic implantation of scaffolds containing growth factors and L-ECM to modulate growth in the normal and regenerating liver.
Division of Gastrointestinal Surgery, Nottingham Digestive Diseases Centre Biomedical Research Unit, University Hospital Nottingham, UK. john.hammond@nottingham.ac.uk
John S
JS
Hammond
Thomas W
TW
Gilbert
Daniel
D
Howard
Abed
A
Zaitoun
George
G
Michalopoulos
Kevin M
KM
Shakesheff
Ian J
IJ
Beckingham
Stephen F
SF
Badylak
D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D002465:Cell Movement; D049109:Cell Proliferation; D004815:Epidermal Growth Factor / Q000502:physiology; D005109:Extracellular Matrix / Q000502:physiology*; D016220:Fibroblast Growth Factor 1 / Q000502:physiology; D016222:Fibroblast Growth Factor 2 / Q000502:physiology; D006498:Hepatectomy; D017228:Hepatocyte Growth Factor / Q000502:physiology; D022781:Hepatocytes / Q000502:physiology*; D036341:Intercellular Signaling Peptides and Proteins / Q000502:physiology*; D008115:Liver Regeneration; D008297:Male; D051381:Rats; D017208:Rats, Wistar
D036341:Intercellular Signaling Peptides and Proteins; D016222:Fibroblast Growth Factor 2; D016220:Fibroblast Growth Factor 1; D004815:Epidermal Growth Factor; D017228:Hepatocyte Growth Factor; D001219:Aspartate Aminotransferases