Genipin crosslinking reduced the immunogenicity of xenogeneic decellularized porcine whole-liver matrices through regulation of immune cell proliferation and polarization.
Decellularized xenogeneic whole-liver matrices are plausible biomedical materials for the bioengineering of liver transplantation. A common method to reduce the inflammatory potential of xenogeneic matrices is crosslinking. Nevertheless, a comprehensive analysis of the immunogenic features of cross-linked decellularized tissue is still lacking. We aimed to reduce the immunogenicity of decellularized porcine whole-liver matrix through crosslinking with glutaraldehyde or genipin, a new natural agent, and investigated the mechanism of the immune-mediated responses. The histologic assessment of the host's immune reaction activated in response to these scaffolds, as well as the M1/M2 phenotypic polarization profile of macrophages, was studied in vivo. The genipin-fixed scaffold elicited a predominantly M2 phenotype response, while the glutaraldehyde-fixed scaffold resulted in disrupted host tissue remodeling and a mixed macrophage polarization profile. The specific subsets of immune cells involved in the responses to the scaffolds were identified in vitro. Crosslinking alleviated the host response by reducing the proliferation of lymphocytes and their subsets, accompanied by a decreased release of both Th1 and Th2 cytokines. Therefore, we conclude that the natural genipin crosslinking could lower the immunogenic potential of xenogeneic decellularized whole-liver scaffolds.
Laboratory of Pathology, West China Hospital, Sichuan University, Chengdu, 610041, China.|Key Laboratory of Transplant Engineering and Immunology, Ministry of Health, West China Hospital, Sichuan University, Chengdu, 610041, China.
Yujia
Y
Wang
Laboratory of Pathology, West China Hospital, Sichuan University, Chengdu, 610041, China.|Key Laboratory of Transplant Engineering and Immunology, Ministry of Health, West China Hospital, Sichuan University, Chengdu, 610041, China.
Ji
J
Bao
Department of General Surgery, The first people's hospital of Yibin, Yibin, 644000, China.
Xiujuan
X
Wu
Laboratory of Pathology, West China Hospital, Sichuan University, Chengdu, 610041, China.|Key Laboratory of Transplant Engineering and Immunology, Ministry of Health, West China Hospital, Sichuan University, Chengdu, 610041, China.
Qiong
Q
Wu
Laboratory of Pathology, West China Hospital, Sichuan University, Chengdu, 610041, China.|Key Laboratory of Transplant Engineering and Immunology, Ministry of Health, West China Hospital, Sichuan University, Chengdu, 610041, China.
Yi
Y
Li
Laboratory of Pathology, West China Hospital, Sichuan University, Chengdu, 610041, China.|Key Laboratory of Transplant Engineering and Immunology, Ministry of Health, West China Hospital, Sichuan University, Chengdu, 610041, China.
Yongjie
Y
Zhou
Laboratory of Pathology, West China Hospital, Sichuan University, Chengdu, 610041, China.|Key Laboratory of Transplant Engineering and Immunology, Ministry of Health, West China Hospital, Sichuan University, Chengdu, 610041, China.
Li
L
Li
Laboratory of Pathology, West China Hospital, Sichuan University, Chengdu, 610041, China.|Key Laboratory of Transplant Engineering and Immunology, Ministry of Health, West China Hospital, Sichuan University, Chengdu, 610041, China.|Department of Pathology, West China Hospital, Sichuan University, Chengdu, 610041, China.
Hong
H
Bu
D064591:Allografts; D000818:Animals; D001672:Biocompatible Materials; D049109:Cell Proliferation; D018920:Coculture Techniques; D016207:Cytokines / Q000378:metabolism; D005109:Extracellular Matrix / Q000378:metabolism*; D064593:Heterografts; D006801:Humans; D007107:Immune System / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D039823:Iridoids / Q000737:chemistry*; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000378:metabolism; D008099:Liver / Q000276:immunology* / Q000378:metabolism*; D016031:Liver Transplantation; D008264:Macrophages / Q000276:immunology / Q000378:metabolism; D013552:Swine; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology / Q000378:metabolism; D023822:Tissue Engineering; D054457:Tissue Scaffolds
D001672:Biocompatible Materials; D016207:Cytokines; D039823:Iridoids; C007834:genipin