Laboratory for Transplantation and Regenerative Medicine, Gothenburg University, Gothenburg, Sweden.
Proteomics Core Facility, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
Tissue Eng Part A. 2020 Nov;26(21-22):1180-1198. doi: 10.1089/ten.TEA.2020.0055. Epub 2020 Sep 29.
The immunogenicity of the extracellular matrix (ECM) from genetically similar (syngeneic) and dissimilar (allogeneic and xenogeneic) species has puzzled the scientific community for many years. After implantation, the literature describes an absorption of ECM material since it is biodegradable. However, no clear insight really exists to substantiate how the underlying immune and biological responses result in absorption of ECM materials. In this context, it is important to characterize infiltrating cells and identify dominant cell populations in the infiltrate. We have studied the immune response in mice after implantation of decellularized (DC) cardiac scaffolds derived from pig and mouse. The polymorphism of the infiltrate into the implanted material signifies the importance of the adaptive immune response that is distinct for xenoimplants and alloimplants. Matrix resorption takes place mainly through phagocytic cells such as mast cells, dendritic cells, and macrophages. Histochemical observations show that innate CD8 T cells develop immune tolerance, whereas proteomic analysis predicts the different T cell progenies for alloscaffolds and xenoscaffolds. The amalgamation of graft tolerance and involvement of both B and T cell populations in the vicinity of the graft could be decisive in wound remodeling and survival of the graft. This challenging area presents potential targets for the development of immune-privileged biomaterials, immune tolerant cells, and therapeutic agents in the future. Impact statement In this study, we have characterized the allogeneic and xenogeneic immune responses for decellularized (DC) cardiac scaffolds. We postulate that although the T cells are important players for immune tolerance of DC graft, the mechanism of their differentiation inside the host is donor specific. In this study, we have reported the distinct immune responses for syngeneic DC scaffolds than allogeneic and xenogeneic scaffolds. This distinct response provides the bases for the different immune responses reported for DC homografts in the literature. This study can provide the greater insight for modification of postimplant strategies to achieve host acceptance of donor extracellular matrix scaffolds.
多年来，同种（同基因）和异种（异基因和异种）来源的细胞外基质（ECM）的免疫原性一直令科学界感到困惑。植入后，文献描述 ECM 材料会被吸收，因为它是可生物降解的。然而，目前并没有明确的认识来证实潜在的免疫和生物学反应如何导致 ECM 材料的吸收。在这种情况下，对浸润细胞进行特征分析并确定浸润中的主要细胞群是很重要的。我们研究了经脱细胞处理的（DC）猪和鼠源性心脏支架植入小鼠后的免疫反应。浸润到植入材料中的多态性表明了适应性免疫反应的重要性，这种反应对于异种和同种移植物是不同的。基质的吸收主要通过吞噬细胞（如肥大细胞、树突状细胞和巨噬细胞）来完成。组织化学观察表明，固有 CD8 T 细胞产生免疫耐受，而蛋白质组学分析预测了同种移植物和异种移植物的不同 T 细胞前体。移植物周围的移植物耐受和 B 细胞和 T 细胞群体的参与可能对创面重塑和移植物存活具有决定性作用。这一具有挑战性的领域为未来免疫特惠生物材料、免疫耐受细胞和治疗剂的发展提供了潜在的靶点。
