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Auxiliary xenotransplantation as an in vivo bioreactor—Development of a transplantable liver graft from a tiny partial liver
Author(s) -
Masano Yuki,
Yagi Shintaro,
Miyachi Yosuke,
Okumura Shinya,
Kaido Toshimi,
Haga Hironori,
Kobayashi Eiji,
Uemoto Shinji
Publication year - 2019
Publication title -
xenotransplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.052
H-Index - 61
eISSN - 1399-3089
pISSN - 0908-665X
DOI - 10.1111/xen.12545
Subject(s) - xenotransplantation , in vivo , liver transplantation , transplantation , liver regeneration , bioartificial liver device , cd31 , parenchyma , biology , regeneration (biology) , pathology , andrology , hepatocyte , immunology , medicine , immunohistochemistry , in vitro , microbiology and biotechnology , biochemistry
Background We established a completely novel method of auxiliary xenogeneic partial liver transplantation and examined whether liver grafts procured from Syrian hamsters regenerated in nude rats, which were used as in vivo bioreactors. Methods The hamsters and the rats were all males (n = 10). Partial liver grafts from hamsters were transplanted into nude rats in an auxiliary manner. We evaluated liver graft injury, rejection, and regeneration during 7 days after auxiliary xenogeneic partial liver transplantation. Results All rats survived until sacrifice on post‐operative day (POD) 1, 3, and 7. HE‐staining showed normal at POD1, mild periportal edema, and slight bile duct and venous endothelial inflammation at POD3, and moderate acute cellular rejection at POD7 without parenchymal necrosis. The liver regeneration rates at POD3 and 7 were 1.54 ± 0.23 and 2.54 ± 0.43, respectively. The Ki‐67 labeling index was also elevated at POD3 (27.5 ± 4.1%). Serum HGF and VEGF were elevated at POD1 and 3. ATP levels of liver grafts recovered at POD7. Conclusions These results revealed that with appropriate immunosuppressive therapy, partial liver graft regeneration occurred in a xenogeneic animal, which suggests liver grafts regenerated in xenogeneic environments, such as an in vivo bioreactor, have potential to be transplantable liver grafts for humans.