Transplantation of bioengineered liver capable of extended function in a preclinical liver failure model

Hisanobu Higashi, Hiroshi Yagi, Kohei Kuroda, Kazuki Tajima, Hideaki Kojima, Kotaro Nishi, Toshinori Morisaku, Kazuya Hirukawa, Kazumasa Fukuda, Kentaro Matsubara, Minoru Kitago, Masahiro Shinoda, Hideaki Obara, Shungo Adachi, Kumiko Nishimura, Tohru Natsume, Masatoshi Tomi, Alejandro Soto-Gutierrez, Yuko Kitagawa

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)731-744
Number of pages14
JournalAmerican Journal of Transplantation
Volume22
Issue number3
DOIs
Publication statusPublished - 2022 Mar

Keywords

  • artificial organs/support devices
  • bioengineering
  • liver transplantation/hepatology
  • regenerative medicine
  • tissue/organ engineering
  • translational research/science

ASJC Scopus subject areas

  • Immunology and Allergy
  • Transplantation
  • Pharmacology (medical)

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