Arzi B, DuRaine G D, Lee C A, Huey D J, Borjesson D L, Murphy B G, Hu J C Y, Baumgarth N, Athanasiou K A
Department of Biomedical Engineering, University of California, Davis, CA, USA; Department of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California, Davis, CA, USA.
Department of Biomedical Engineering, University of California, Davis, CA, USA.
Acta Biomater. 2015 Sep;23:72-81. doi: 10.1016/j.actbio.2015.05.025. Epub 2015 May 28.
The ability to repair damaged cartilage is a major goal of musculoskeletal tissue engineering. Allogeneic (same species, different individual) or xenogeneic (different species) sources can provide an attractive source of chondrocytes for cartilage tissue engineering, since autologous (same individual) cells are scarce. Immune rejection of non-autologous hyaline articular cartilage has seldom been considered due to the popular notion of "cartilage immunoprivilege". The objective of this study was to determine the suitability of allogeneic and xenogeneic engineered neocartilage tissue for cartilage repair. To address this, scaffold-free tissue engineered articular cartilage of syngeneic (same genetic background), allogeneic, and xenogeneic origin were implanted into two different locations of the rabbit knee (n=3 per group/location). Xenogeneic engineered cartilage and control xenogeneic chondral explants provoked profound innate inflammatory and adaptive cellular responses, regardless of transplant location. Cytological quantification of immune cells showed that, while allogeneic neocartilage elicited an immune response in the patella, negligible responses were observed when implanted into the trochlea; instead the responses were comparable to microfracture-treated empty defect controls. Allogeneic neocartilage survived within the trochlea implant site and demonstrated graft integration into the underlying bone. In conclusion, the knee joint cartilage does not represent an immune privileged site, strongly rejecting xenogeneic but not allogeneic chondrocytes in a location-dependent fashion. This difference in location-dependent survival of allogeneic tissue may be associated with proximity to the synovium.
Through a series of in vivo studies this research demonstrates that articular cartilage is not fully immunoprivileged. In addition, we now show that anatomical location of the defect, even within the same joint compartment, strongly influences the degree of the resultant immune response. This is one of the first investigations to show that (1) immune tolerance to allogeneic tissue engineered cartilage and (2) subsequent implant survival are dependent on the implant location and proximity to the synovium.
修复受损软骨的能力是肌肉骨骼组织工程的一个主要目标。同种异体（同一物种，不同个体）或异种（不同物种）来源可为软骨组织工程提供有吸引力的软骨细胞来源，因为自体（同一个体）细胞稀缺。由于“软骨免疫赦免”这一普遍观念，非自体透明关节软骨的免疫排斥很少被考虑。本研究的目的是确定同种异体和异种工程化新生软骨组织用于软骨修复的适用性。为解决这一问题，将同基因（相同遗传背景）、同种异体和异种来源的无支架组织工程关节软骨植入兔膝关节的两个不同部位（每组/每个部位n = 3）。无论移植位置如何，异种工程化软骨和对照异种软骨外植体都会引发强烈的先天性炎症和适应性细胞反应。免疫细胞的细胞学定量分析表明，虽然同种异体新生软骨在髌骨中引发了免疫反应，但植入滑车时观察到的反应可忽略不计；相反，其反应与微骨折治疗的空缺损对照相当。同种异体新生软骨在滑车植入部位存活，并显示移植物与下方骨整合。总之，膝关节软骨不代表免疫赦免部位，以位置依赖的方式强烈排斥异种但不排斥同种异体软骨细胞。同种异体组织在位置依赖的存活方面的这种差异可能与滑膜的接近程度有关。
通过一系列体内研究，本研究表明关节软骨并非完全免疫赦免。此外，我们现在表明，缺损的解剖位置，即使在同一关节腔内，也会强烈影响由此产生的免疫反应程度。这是首批表明（1）对同种异体组织工程软骨的免疫耐受性和（2）随后的植入物存活取决于植入位置和与滑膜的接近程度的研究之一。
