Extracellular matrix-enriched polymeric scaffolds as a substrate for hepatocyte cultures: in vitro and in vivo studies.
Tissue engineering is a promising approach to developing hepatic tissue suitable for the functional replacement of a failing liver. The aim of the present study was to investigate whether an extracellular cell matrix obtained from fibroblasts-cultured within scaffolds of hyaluronic acid (HYAFF) could influence the proliferation rate and survival of rat hepatocytes both during long-term culture and after in vivo transplantation. Cultures were evaluated by histological and morphological analysis, a proliferation assay and metabolic activity (albumin secretion). Hepatocytes cultured in extracellular matrix-enriched scaffolds exhibited a round cellular morphology and re-established cell-cell contacts, growing into aggregates of several cells along and/or among fibers in the fabric. Hepatocytes were able to secrete albumin up to 14 days in culture. In vivo results demonstrated the biocompatibility of HYAFF-11 implanted in nude mice, in which hepatocytes maintained small well-organised aggregates until the 35th day. In conclusion, the presence of a fibroblast-secreted extracellular matrix improved the biological properties of the hyaluronan scaffold, favoring the survival and morphological integrity of hepatocytes in vitro and in vivo.
Department of Histology, Microbiology and Medical Biotecnology, University of Padova, Italy. barbara.zavan@unipd.it
B
B
Zavan
P
P
Brun
V
V
Vindigni
A
A
Amadori
W
W
Habeler
P
P
Pontisso
D
D
Montemurro
G
G
Abatangelo
R
R
Cortivo
D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry; D018929:Cell Culture Techniques / Q000379:methods; D049109:Cell Proliferation; D002470:Cell Survival / Q000502:physiology; D002478:Cells, Cultured; D005109:Extracellular Matrix / Q000378:metabolism*; D005347:Fibroblasts / Q000378:metabolism*; D022781:Hepatocytes / Q000166:cytology* / Q000502:physiology / Q000637:transplantation*; D006801:Humans; D006820:Hyaluronic Acid / Q000737:chemistry*; D019164:Liver, Artificial; D008422:Materials Testing; D051379:Mice; D016513:Mice, SCID; D051381:Rats; D017208:Rats, Wistar; D023822:Tissue Engineering / Q000379:methods*
D001672:Biocompatible Materials; D006820:Hyaluronic Acid