TY - JOUR
T1 - Transplantation of bioengineered liver capable of extended function in a preclinical liver failure model
AU - Higashi, Hisanobu
AU - Yagi, Hiroshi
AU - Kuroda, Kohei
AU - Tajima, Kazuki
AU - Kojima, Hideaki
AU - Nishi, Kotaro
AU - Morisaku, Toshinori
AU - Hirukawa, Kazuya
AU - Fukuda, Kazumasa
AU - Matsubara, Kentaro
AU - Kitago, Minoru
AU - Shinoda, Masahiro
AU - Obara, Hideaki
AU - Adachi, Shungo
AU - Nishimura, Kumiko
AU - Natsume, Tohru
AU - Tomi, Masatoshi
AU - Soto-Gutierrez, Alejandro
AU - Kitagawa, Yuko
N1 - Publisher Copyright:
© 2021 The American Society of Transplantation and the American Society of Transplant Surgeons
PY - 2022/3
Y1 - 2022/3
N2 - Unlimited organ availability would represent a paradigm shift in transplantation. Long-term in vivo engraftment and function of scaled-up bioengineered liver grafts have not been previously reported. In this study, we describe a human-scale transplantable liver graft engineered on a porcine liver-derived scaffold. We repopulated the scaffold parenchyma with primary hepatocytes and the vascular system with endothelial cells. For in vivo functional testing, we performed auxiliary transplantation of the repopulated scaffold in pigs with induced liver failure. It was observed that the auxiliary bioengineered liver graft improved liver function for 28 days and exhibited upregulation of liver-specific genes. This study is the first of its kind to present 28 days of posttransplant evaluation of a bioengineered liver graft using a preclinical large animal model. Furthermore, it provides definitive evidence for the feasibility of engineering human-scale transplantable liver grafts for clinical applications.
AB - Unlimited organ availability would represent a paradigm shift in transplantation. Long-term in vivo engraftment and function of scaled-up bioengineered liver grafts have not been previously reported. In this study, we describe a human-scale transplantable liver graft engineered on a porcine liver-derived scaffold. We repopulated the scaffold parenchyma with primary hepatocytes and the vascular system with endothelial cells. For in vivo functional testing, we performed auxiliary transplantation of the repopulated scaffold in pigs with induced liver failure. It was observed that the auxiliary bioengineered liver graft improved liver function for 28 days and exhibited upregulation of liver-specific genes. This study is the first of its kind to present 28 days of posttransplant evaluation of a bioengineered liver graft using a preclinical large animal model. Furthermore, it provides definitive evidence for the feasibility of engineering human-scale transplantable liver grafts for clinical applications.
KW - artificial organs/support devices
KW - bioengineering
KW - liver transplantation/hepatology
KW - regenerative medicine
KW - tissue/organ engineering
KW - translational research/science
UR - http://www.scopus.com/inward/record.url?scp=85122318663&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85122318663&partnerID=8YFLogxK
U2 - 10.1111/ajt.16928
DO - 10.1111/ajt.16928
M3 - Article
C2 - 34932270
AN - SCOPUS:85122318663
SN - 1600-6135
VL - 22
SP - 731
EP - 744
JO - American Journal of Transplantation
JF - American Journal of Transplantation
IS - 3
ER -