Department of Transplantation Surgery, Laboratory for Transplantation and Regenerative Medicine, Sahlgrenska University Hospital, Gothenburg University, Gothenburg, Sweden.
Department of Laboratory Medicine, Proteomic Hematology, Lund Stem Cell Center, Lund University, Lund, Sweden.
Tissue Eng Part A. 2022 Jul;28(13-14):621-639. doi: 10.1089/ten.TEA.2021.0146. Epub 2022 Jun 21.
Biological scaffold is a popular choice for the preparation of tissue-engineered organs and has the potential to address donor shortages in clinics. However, biological scaffolds prepared by physical or chemical agents cause damage to the extracellular matrix (ECM) by potentially inducing immune responses after implantation. The current study explores the fate of the decellularized (DC) scaffolds using a cocktail of chemicals following implantation without using immunosuppressants. Using the syngeneic (Lewis male-Lewis female) and allogeneic (Brown Norway male-Lewis female) models and different tissue routes (subcutaneous omentum) for implantation, we applied in-depth quantitative proteomics, genomics along with histology and quantitative image analysis tools to comprehensively describe and compare the proteins following DC and postimplantation. Our data helped to identify any alteration postdecullarization as well implantation. We could also monitor route-specific modulation of the ECM and regulation of the immune responses (macrophage and T cells) following implantation. The current approach opens up the possibility to monitor the fate of biological scaffolds in terms of the ECM and immune response against the implants. In addition, the identification of different routes helped us to identify differential immune responses against the implants. This study opens up the potential to identify the changes associated with chemical DC both pre- and postimplantation, which could further help to promote research in this direction. Impact Statement The development of a biological scaffold helps in the preparation of a functional organ in the clinics. In the current study, we develop a strategy for chemical decellularization and explored two different routes to understand the differential responses elicited postimplantation. The use of sensitive protein and genomic tools to study the changes creates a favorable environment for similar efforts to develop and characterize biological scaffolds before further trials in the clinics. The current study, which was carried out without any immunosuppressive agents, could help to establish (a) appropriate chemical strategies for preparing biological scaffolds as well as (b) identify putative implantable routes to circumvent any adverse immune reactions, which will ultimately decide the outcome for acceptance or rejection of the scaffold/implant.
生物支架是制备组织工程器官的热门选择，有潜力解决临床供体短缺的问题。然而，通过物理或化学试剂制备的生物支架在植入后可能会引起免疫反应，从而对细胞外基质（ECM）造成损伤。本研究探索了在不使用免疫抑制剂的情况下，使用化学鸡尾酒处理脱细胞（DC）支架后的命运。我们使用同基因（Lewis 雄性-Lewis 雌性）和异基因（Brown Norway 雄性-Lewis 雌性）模型以及不同的组织途径（皮下大网膜）进行植入，并应用深度定量蛋白质组学、基因组学以及组织学和定量图像分析工具，全面描述和比较 DC 后和植入后的蛋白质。我们的数据有助于识别脱细胞化后和植入后的任何变化。我们还可以监测植入后 ECM 的特定途径调节和免疫反应（巨噬细胞和 T 细胞）的调节。目前的方法为监测生物支架在 ECM 和对植入物的免疫反应方面的命运提供了可能性。此外，不同途径的鉴定有助于我们识别针对植入物的不同免疫反应。这项研究为识别与化学 DC 相关的变化开辟了可能性，这可能有助于进一步推动这一方向的研究。 影响陈述 生物支架的发展有助于在临床上制备功能性器官。在本研究中，我们开发了一种化学去细胞化的策略，并探索了两种不同的途径，以了解植入后的差异反应。使用敏感的蛋白质和基因组工具来研究变化为在临床前进一步试验之前开发和表征生物支架创造了有利的环境。本研究在不使用任何免疫抑制剂的情况下进行，有助于建立 (a) 用于制备生物支架的适当化学策略，以及 (b) 确定潜在的可植入途径，以避免任何不良的免疫反应，这最终将决定支架/植入物的接受或拒绝的结果。
