Treatment of acute liver failure in mice by hepatocyte xenotransplantation.
Liver diseases still have a high mortality even though liver transplantation has become a standard treatment. Currently, hepatocyte transplantation has been proposed as another promising strategy. One limitation is the availability of human livers as a source of hepatocytes. Because of an unlimited supply, the use of porcine hepatocytes might address this problem. Regardless of the source, once isolated hepatocytes lose specific functionality due to the loss of the natural microenvironment. For this reason, we tested the ability of a self-assembling peptide nanofiber (SAPNF) to provide a provisional three-dimensional (3D) support to interact with cells to control their function in vivo. Isolated porcine hepatocytes were embedded in SAPNF, or collagen type I and transplanted by direct injection into the splenic pulp of SCID mice suffering from acute liver failure (ALF) by 90% hepatectomy. SAPNF porcine hepatocyte transplantation produced engraftment that was far superior to that obtained using collagen and prolonged the survival of mice with ALF, in contrast with controls. An ultrastructural evaluation using transmission electron microscopy indicated extensive cell-cell communication and preservation of hepatocyte architecture. The transplanted SAPNF hepatocytes showed higher expression of albumin and PAS and lower apoptotic events assessed by TUNEL staining. Hepatocytes culture in a truly 3D network allows in vivo maintaining of differentiated functions, and once transplanted between widely divergent species can function to correct acute liver failure in mice and prolong their survival.
Yamamoto
Tsuyoshi
T
Department of Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan.
Navarro-Alvarez
Nalú
N
Soto-Gutierrez
Alejandro
A
Yuasa
Takeshi
T
Iwamuro
Masaya
M
Kubota
Yasuhiro
Y
Seita
Masayuki
M
Kawamoto
Hironobu
H
Javed
Shahid M
SM
Kondo
Eisaku
E
Noguchi
Hirofumi
H
Kobayashi
Satoru
S
Nakaji
Shuhei
S
Kobayashi
Naoya
N
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects; D006498:Hepatectomy; D022781:Hepatocytes / Q000166:cytology / Q000378:metabolism / Q000637:transplantation* / Q000648:ultrastructure; D017114:Liver Failure, Acute / Q000628:therapy*; D051379:Mice; D016513:Mice, SCID; D057139:Nanofibers / Q000737:chemistry; D010455:Peptides / Q000494:pharmacology; D012038:Regeneration / Q000187:drug effects; D013154:Spleen / Q000187:drug effects / Q000473:pathology; D016019:Survival Analysis; D034421:Sus scrofa; D014183:Transplantation, Heterologous
D010455:Peptides