Whole organ tissue engineering is a promising approach to address organ shortages in many applications, including lung transplantation for patients with chronic pulmonary disease. Engineered lungs may be derived from animal sources after removing cellular content, exposing the extracellular matrix to serve as a scaffold for recellularization with human cells. However, the use of xenogeneic tissue sources in human transplantation raises concerns due to the presence of the antigenic Gal epitope. In the present study, lungs from wild type or α-Gal knockout pigs were harvested, decellularized, and implanted subcutaneously in a non-human primate model to evaluate the host immune response. The decellularized porcine implants were compared to a sham surgery control, as well as native porcine and decellularized macaque lung implants. The results demonstrated differential profiles of circulating and infiltrating immune cell subsets and histological outcomes depending on the implanted tissue source. Upon implantation, the decellularized α-Gal knockout lung constructs performed similarly to the decellularized wild type lung constructs. However, upon re-implantation into a chronic exposure model, the decellularized wild type lung constructs resulted in a greater proportion of infiltrating CD45⁺ cells, including CD3⁺ and CD8⁺ cytotoxic T-cells, likely mediated by an increase in production of Gal-specific antibodies. The results suggest that removal of the Gal epitope can potentially reduce adverse inflammatory reactions associated with chronic exposure to engineered organs containing xenogeneic components.

全器官组织工程学是解决许多应用中器官短缺的有前途的方法，包括慢性肺病患者的肺移植。去除细胞内含物，暴露出细胞外基质以用作人细胞再细胞化的支架后，工程肺可能来源于动物。然而，由于抗原Gal表位的存在，异种组织来源在人类移植中的使用引起了人们的关注。在本研究中，从野生型或α-Gal基因敲除猪的肺中收集，脱细胞并皮下植入非人灵长类动物模型中，以评估宿主的免疫反应。将脱细胞的猪植入物与假手术对照以及天然猪和脱细胞的猕猴肺植入物进行比较。结果证明了循环和浸润免疫细胞亚群的不同情况以及组织学结果取决于植入的组织来源。植入后，脱细胞的α-Gal敲除肺构建体的表现与脱细胞的野生型肺构建体相似。然而，在重新植入慢性暴露模型后，脱细胞的野生型肺构建体导致更大比例的浸润CD45⁺细胞，包括CD3 ⁺和CD8 ⁺细胞毒性T细胞，可能是由Gal特异性抗体产生的增加介导的。结果表明，Gal表位的去除可以潜在地减少与长期暴露于含有异种成分的工程器官相关的不良炎症反应。