De novo liver tissue formation in rats using a novel collagen-polypropylene scaffold.
In experimental and clinical settings hepatocyte transplantation has provided limited benefit to patients with chronic liver disease because the transplanted hepatocytes were short-lived and were merely maintained for a brief period within the body. Except for whole-liver transplantation, creation of de novo liver tissue is necessary to treat this condition on a long-term basis. The aim of this study was to facilitate the formation of new tissue by actual self-regeneration, rather than by compensatory hypertrophy, or scar formation, with our collagen-polypropylene composite scaffold. Collagen-polypropylene composite scaffolds, not containing hepatocytes, were implanted into the median liver lobe and the dynamics of new liver tissue formation was analyzed immunohistochemically over a 6-month period. Control scaffolds consisted of polypropylene scaffolds without collagen matrix. The control scaffold implants remained hollow throughout the study period and became encapsulated with a hard connective tissue capsule 1 week after implantation. In contrast, the collagen-polypropylene composite scaffold was filled with regenerating tissue structures 3 weeks after implantation. At this time, the predominant cell type within the scaffold was sesmin-positive stellate cells. A week earlier, oval cells were identified using monoclonal antibody staining (OV-6). Subsequently, these cells differentiated into alpha-fetoprotein-positive immature hepatocytes. After 6 months, mature liver tissue, juxtaposed with bile ducts and blood vessels, was seen within the polypropylene scaffolds. We report the first evidence of de novo formation of liver tissue within a polypropylene scaffold, following implantation in the liver. This scaffold may play a role in treating chronic liver diseases requiring organ replacement therapy.
Takimoto
Yukinobu
Y
University of California, Los Angeles, Department of Medicine, Division of Digestive Diseases, UCLA School of Medicine, Center for the Health Sciences, Los Angeles, CA 90095-7019, USA.
Dixit
Vivek
V
Arthur
Marika
M
Gitnick
Gary
G
D000818:Animals; D003094:Collagen / Q000494:pharmacology* / Q000627:therapeutic use; D015194:Diffusion Chambers, Culture / Q000295:instrumentation / Q000379:methods; D022781:Hepatocytes / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D020007:Implants, Experimental; D008099:Liver / Q000166:cytology / Q000502:physiology* / Q000601:surgery; D008115:Liver Regeneration / Q000187:drug effects / Q000502:physiology*; D008297:Male; D011126:Polypropylenes / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D017208:Rats, Wistar; D023822:Tissue Engineering / Q000295:instrumentation* / Q000379:methods
D011126:Polypropylenes; D003094:Collagen