Ectopic expansion and vascularization of engineered hepatic tissue based on heparinized acellular liver matrix and mesenchymal stromal cell spheroids.

Autor: Wu Q; Laboratory of Pathology, Key Laboratory of Transplant Engineering and Immunology, West China Hospital, Sichuan University, 37# Guoxue Road, Chengdu, Sichuan Province 610041, China; Laboratory of Liver Transplantation, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, China., Li Y; Laboratory of Pathology, Key Laboratory of Transplant Engineering and Immunology, West China Hospital, Sichuan University, 37# Guoxue Road, Chengdu, Sichuan Province 610041, China; Precision Medicine Key Laboratory, West China Hospital, Sichuan University, China., Yang Z; Core Facility of West China Hospital, Sichuan University, China., Li L; Laboratory of Pathology, Key Laboratory of Transplant Engineering and Immunology, West China Hospital, Sichuan University, 37# Guoxue Road, Chengdu, Sichuan Province 610041, China., Yang J; Department of Hepato-Biliary-Pancreatic Surgery, West China Hospital, Sichuan University, China., Zhu X; Laboratory of Pathology, Key Laboratory of Transplant Engineering and Immunology, West China Hospital, Sichuan University, 37# Guoxue Road, Chengdu, Sichuan Province 610041, China., Liu Y; Department of Burn and Plastic Surgery, West China Hospital, Sichuan University, China., Bao J; Laboratory of Pathology, Key Laboratory of Transplant Engineering and Immunology, West China Hospital, Sichuan University, 37# Guoxue Road, Chengdu, Sichuan Province 610041, China. Electronic address: baoji@scu.edu.cn., Bu H; Laboratory of Pathology, Key Laboratory of Transplant Engineering and Immunology, West China Hospital, Sichuan University, 37# Guoxue Road, Chengdu, Sichuan Province 610041, China; Department of Pathology, West China Hospital, Sichuan University, China. Electronic address: hongbu@scu.edu.cn.
Jazyk: angličtina
Zdroj: Acta biomaterialia [Acta Biomater] 2022 Jan 01; Vol. 137, pp. 79-91. Date of Electronic Publication: 2021 Oct 19.
DOI: 10.1016/j.actbio.2021.10.017
Abstrakt: Engineered liver organogenesis is not yet a viable therapeutic option, but ectopic liver histogenesis may be possible. Accumulating evidence has suggested that cell-cell interactions and cell-matrix interactions play an important role in determining the properties of engineered hepatic tissue in vitro and in vivo. In the current study, we utilized heparinized decellularized liver scaffolds and bone marrow mesenchymal stromal cell spheroids to fabricate engineered hepatic tissue, which was subsequently implanted into the omentum of Sprague-Dawley rats with or without liver injury. The survival, liver-specific functions, differentiation level and regenerative potential of the implanted hepatocyte-like cells in this ectopic liver system were evaluated, together with the vascularization status and therapeutic potential of the engineered hepatic tissue. We demonstrated that these hepatic grafts could survive and possess hepatocyte specific function in this ectopic liver system but could also efficiently anastomose with host vascular networks. Furthermore, we found that hepatocyte-like cells within grafts expanded more than 9-fold over the course of 4 weeks in immunocompetent rats with injured livers. Immunostaining revealed that these hepatocyte-like cells could self-organize into cord-like structures in vivo. In addition, these hepatic grafts exhibited therapeutic potential in liver injury induced by CCl 4 . To our knowledge, this is the first report demonstrating the generation of long-term vascularized hepatic parenchyma at ectopic sites based on decellularized liver scaffolds and stem cells. These results provide an economic and feasible method for engineering hepatic tissue from construction to transplantation. This methodology may be applicable in clinical medicine, especially metabolic liver diseases. STATEMENT OF SIGNIFICANCE: In this manuscript, we presented an optimized method for the hepatic engineered tissue (HET) from construction to transplantation. The core of this method is utilizing the combination of heparinized decellularized liver scaffolds and stem cell spheroids, which could provide necessary cell-cell and cell-extracellular matrix interactions for HET in vitro and in vivo. We proved that these hepatic grafts could possess hepatocyte specific function and exhibit strong proliferative activity in ectopic liver system, but also able to anastomose with the host vascular networks efficiently and be compatible with the host immune system. This methodology may be possible one day to apply in clinical medicine, especially metabolic liver diseases.
Competing Interests: Declaration of Competing Interest The authors who have taken part in this study declared that they do not have anything to disclose regarding funding or conflict of interest with respect to this manuscript.
(Copyright © 2021. Published by Elsevier Ltd.)
Databáze: MEDLINE
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