猪半月板单细胞测序揭示了参与干性维持和血管化的高活性红区软骨细胞群

半月板损伤较为常见, 但现有治疗方法难以实现完全治愈。 本研究使用猪作为半月板退化的生物模型, 为半月板损伤前沿性疗法的发展提供支持。 本研究展示的半月板单细胞转录组图谱由对应的四种主要类型细胞簇组成, 包括软骨细胞、内皮细胞、平滑肌细胞和免疫细胞; 并对五个不同软骨细胞亚群 (CH0–CH4) 进行了注释, 其中只有一个在红色和白色区域普遍存在, 表明该区域细胞组成存在显著差异。 白色区域特有的亚群可能负责软骨特异性基质沉积以及保护其免受不良微环境因素的影响; 而红色区域亚群则表现出间充质干细胞的特征, 更有可能与增殖和迁移有关。 此外, 它们还可诱导其他软骨细胞亚群的重塑作用, 促进内皮细胞的增殖和成熟, 诱导愈合和血管的形成过程。 由于具备实质性的重塑能力, 这些亚群或许会引起组织工程领域的研究兴趣。 本研究进一步表明, 猪的半月板细胞组成与人类高度相似, 这使其有望成为骨科治疗领域的重要动物模型, 为相关研究提供支持。

Meniscus injuries are widespread and the available treatments do not offer enough healing potential. Here, we provide critical support for using pigs as a biological model for meniscal degeneration and the development of cutting-edge therapies in orthopedics. We present a single-cell transcriptome atlas of the meniscus, consisting of cell clusters corresponding to four major cell types: chondrocytes, endothelial cells, smooth muscle cells, and immune cells. Five distinct chondrocyte subclusters (CH0–CH4) were annotated, of which only one was widespread in both the red and white zones, indicating a major difference in the cellular makeup of the zones. Subclusters distinct to the white zone appear responsible for cartilage-specific matrix deposition and protection against adverse microenvironmental factors, while those in the red zone exhibit characteristics of mesenchymal stem cells and are more likely to proliferate and migrate. Additionally, they induce remodeling actions in other chondrocyte subclusters and promote the proliferation and maturation of endothelial cells, inducing healing and vascularization processes. Considering that they have substantial remodeling capabilities, these subclusters should be of great interest for tissue engineering studies. We also show that the cellular makeup of the pig meniscus is comparable to that of humans, which supports the use of pigs as a model in orthopedic therapy development.