Transplantation of bioengineered liver capable of extended function in a preclinical liver failure model. Issue 3 (5th January 2022)

• Record Type: Journal Article
• Authors: Higashi, Hisanobu; Yagi, Hiroshi; Kuroda, Kohei; Tajima, Kazuki; Kojima, Hideaki; Nishi, Kotaro; Morisaku, Toshinori; Hirukawa, Kazuya; Fukuda, Kazumasa; Matsubara, Kentaro; Kitago, Minoru; Shinoda, Masahiro; Obara, Hideaki; Adachi, Shungo; Nishimura, Kumiko; Natsume, Tohru; Tomi, Masatoshi; Soto‐Gutierrez, Alejandro; Kitagawa, Yuko
• Is Part Of: American journal of transplantation. Volume 22:Issue 3(2022)
• Page Start: 731
• Page End: 744
• Publication Date: 2022-01-05
• Subjects: artificial organs/support devices -- bioengineering -- liver transplantation/hepatology -- regenerative medicine -- tissue/organ engineering -- translational research/science; Transplantation of organs, tissues, etc -- Periodicals; 617.95
• DOI: 10.1111/ajt.16928
• Languages: English
• ISSNs: 1600-6135

Abstract

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. Abstract : A bioengineered liver graft based on a native organ scaffold provides therapeutic function in a large animal model of liver failure.