Tissue Engineering and Cell Therapy Group, Singapore Eye Research Institute, Singapore, 169856, Singapore.
Ophthalmology and Visual Sciences Academic Clinical Programme, Duke-NUS Medical School, Singapore, 169857, Singapore.
Nat Commun. 2024 Jun 11;15(1):4959. doi: 10.1038/s41467-024-49008-3.
Intrastromal cell therapy utilizing quiescent corneal stromal keratocytes (qCSKs) from human donor corneas emerges as a promising treatment for corneal opacities, aiming to overcome limitations of traditional surgeries by reducing procedural complexity and donor dependency. This investigation demonstrates the therapeutic efficacy of qCSKs in a male rat model of corneal stromal opacity, underscoring the significance of cell-delivery quality and keratocyte differentiation in mediating corneal opacity resolution and visual function recovery. Quiescent CSKs-treated rats display improvements in escape latency and efficiency compared to wounded, non-treated rats in a Morris water maze, demonstrating improved visual acuity, while stromal fibroblasts-treated rats do not. Advanced imaging, including multiphoton microscopy, small-angle X-ray scattering, and transmission electron microscopy, revealed that qCSK therapy replicates the native cornea's collagen fibril morphometry, matrix order, and ultrastructural architecture. These findings, supported by the expression of keratan sulfate proteoglycans, validate qCSKs as a potential therapeutic solution for corneal opacities.
利用来自人供体角膜的静止性角膜基质角膜细胞(qCSKs)的间质细胞疗法作为治疗角膜混浊的一种有前途的方法,旨在通过降低手术复杂性和对供体的依赖来克服传统手术的局限性。本研究在雄性大鼠角膜基质混浊模型中证明了 qCSKs 的治疗效果,突出了细胞传递质量和角膜细胞分化在介导角膜混浊消退和视觉功能恢复中的重要性。在 Morris 水迷宫中,与受伤、未经治疗的大鼠相比,接受 qCSK 治疗的大鼠在逃避潜伏期和效率方面均有改善,表明视力提高,而接受基质成纤维细胞治疗的大鼠则没有。高级成像技术,包括多光子显微镜、小角 X 射线散射和透射电子显微镜,显示 qCSK 治疗复制了天然角膜的胶原纤维形态计量学、基质有序性和超微结构。这些发现得到硫酸角质素蛋白聚糖表达的支持,证明 qCSKs 是治疗角膜混浊的一种潜在治疗方法。