Abstract
Cell-based therapy has been proposed as an alternative to orthotopic liver transplantation. The novel transplantation of an in vitro-generated liver bud might have therapeutic potential. In vivo and ex vivo methods for growing a liver bud are essential for paving the way for the clinical translation of liver bud transplantation. We herein report a novel transplantation method for liver buds that are grown in vivo involving orthotopic transplantation on the transected parenchyma of the liver, which showed long engraftment and marked growth in comparison to heterotopic transplantation. Furthermore, this study demonstrates a method for rapidly fabricating scalable liver-like tissue by fusing hundreds of liver bud-like spheroids using a 3D bioprinter. Its system to fix the shape of the 3D tissue with the needle-array system enabled the fabrication of elaborate geometry and the immediate execution of culture circulation after 3D printing—thereby avoiding an ischemic environment ex vivo. The ex vivo-fabricated human liver-like tissue exhibited self-tissue organization ex vivo and engraftment on the liver of nude rats. These achievements conclusively show both in vivo and ex vivo methods for growing in vitro-generated liver buds. These methods provide a new approach for in vitro-generated liver organoids transplantation.
Highlights
Half a century has passed since the first human liver transplantation was performed
A further study to bridge the gap between the real and the engineered liver organoid is necessary, the results of the present study support the idea that orthotopic transplantation provides a hospitable environment for liver tissue engraftment and shows a new approach to cell-based therapy, which may lead to tissue transplantation in the liver
We report two novel methods for growing in vitro-generated liver buds in vivo and ex vivo: orthotopic transplantation on the transected liver parenchyma to directly connect the transplant with the native liver tissue; and the biofabrication of a scalable liver-like tissue through the 3D bioprinting of LBSs
Summary
Half a century has passed since the first human liver transplantation was performed. While orthotopic liver transplantation (OLT) has become a definitive treatment for end-stage liver disease, a shortage of organ donors has limited its benefit[1]. We developed a new method for the orthotopic transplantation of liver buds that directly connects the transplant to the recipient’s native liver. Various technologies for assembling cellular aggregates to fabricate 3D tissues (with or without a scaffold) have been reported[14,15] These technologies have some disadvantages, including several problems that are associated with the exogenous materials of the scaffold[16], low physiological strength, and the conditions of tissue culture. A further study to bridge the gap between the real and the engineered liver organoid is necessary, the results of the present study support the idea that orthotopic transplantation provides a hospitable environment for liver tissue engraftment and shows a new approach to cell-based therapy, which may lead to tissue transplantation in the liver
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