Menarim Bruno C, Mok Chan Hee, Scoggin Kirsten E, Gornik Alexis, Adam Emma N, Loux Shavahn C, MacLeod James N
Gluck Equine Research Center, Department of Veterinary Science, Martin-Gatton College of Agriculture, Food and Environment, University of Kentucky, Lexington, Kentucky.
Department of Orthopedic Surgery, School of Medicine, University of California San Francisco, San Francisco, California.
JB JS Open Access. 2025 Jan 15;10(1). doi: 10.2106/JBJS.OA.24.00043. eCollection 2025 Jan-Mar.
Therapies for cartilage restoration are of great interest, but current options provide limited results. In salamanders, interzone (IZN) tissue can regenerate large joint lesions. The mammalian homolog to this tissue exists during fetal development and exhibits remarkable chondrogenesis in vitro. This study analyzed the potential of equine IZN and adjacent anlagen (ANL) cells to regenerate osteochondral defects.
Osteochondral defects were created in the knee of immunosuppressed rats and were grafted with cell pellets from either equine fetal IZN, equine fetal ANL, adult fibroblasts, or adult chondrocytes, or they were left untreated. Osteochondral repair was assessed after 2, 6, and 16 weeks.
Untreated lesions unexpectedly failed to represent critical-sized defects and at 2 weeks exhibited new subchondral bone covered by a fibrocartilage layer that thinned over time. Fibroblast-treated defects filled with soft fibrous tissue. Chondrocyte-treated repair tissue exhibited strong proteoglycan and COL2 staining but poor integration to the adjacent bone. Defects treated with IZN, ANL, or chondrocyte pellets developed hyaline cartilage with increasing safranin-O and collagen II staining over time. IZN and ANL repair tissues exhibited some evidence of zonal architecture such as native cartilage and the best bone integration; nonetheless, they developed exuberant growth, often causing patellar instability and osteoarthritis.
IZN or ANL cells exhibited some potential to recapitulate developmental features during cartilage repair. However, identifying regulatory determinants of IZN and ANL-derived overgrowths is necessary.
Studies grafting IZN or ANL tissues in larger animal models with regular immune functions may provide additional insights into improving osteochondral regeneration.
软骨修复疗法备受关注，但目前的治疗方法效果有限。在蝾螈中，中间带（IZN）组织能够再生大型关节损伤。这种组织在哺乳动物胎儿发育过程中存在同源物，并且在体外表现出显著的软骨生成能力。本研究分析了马IZN和相邻原基（ANL）细胞再生骨软骨缺损的潜力。
在免疫抑制大鼠的膝关节制造骨软骨缺损，并用来自马胎儿IZN、马胎儿ANL、成年成纤维细胞或成年软骨细胞的细胞团块进行移植，或者不进行处理。在2周、6周和16周后评估骨软骨修复情况。
未处理的损伤意外地未表现出临界尺寸缺损，在2周时显示出由纤维软骨层覆盖的新的软骨下骨，该纤维软骨层随时间变薄。成纤维细胞处理的缺损充满了柔软的纤维组织。软骨细胞处理的修复组织显示出强烈的蛋白聚糖和COL2染色，但与相邻骨的整合较差。用IZN、ANL或软骨细胞团块处理的缺损随着时间的推移出现了透明软骨，番红O和胶原蛋白II染色增加。IZN和ANL修复组织表现出一些带状结构的证据，如天然软骨，并且骨整合最佳；尽管如此，它们出现了过度生长，常常导致髌骨不稳定和骨关节炎。
IZN或ANL细胞在软骨修复过程中表现出一些重现发育特征的潜力。然而，确定IZN和ANL衍生的过度生长的调节决定因素是必要的。
在具有正常免疫功能的大型动物模型中移植IZN或ANL组织的研究可能为改善骨软骨再生提供更多见解。
