Wei Ying, Ma Cong, An Chuanfeng, Zhang Yujie, Zhang Haoyue, Li Qiyou, Kong Li, Wang Huanan, Ma Xiang
Department of Ophthalmology, The First Affiliated Hospital of Dalian Medical University, Dalian, 116014, China.
MOE Key Laboratory of Bio-Intelligent Manufacturing, Dalian Key Laboratory of Artificial Organ and Regenerative Medicine, School of Bioengineering, Dalian University of Technology, Dalian, 116024, China.
Mater Today Bio. 2025 May 23;32:101880. doi: 10.1016/j.mtbio.2025.101880. eCollection 2025 Jun.
Retinal pigment epithelial (RPE) cells are specialized neural cells crucial for vision, while human embryonic stem cell-derived retinal pigment epithelial (hESC-RPE) cells hold great potential as a viable cell source for treating retinal degenerative diseases like retinitis pigmentosa (RP). However, the transplantation efficiency and viability of hESC-RPE cell suspensions are relatively low due to detrimental shear-force during operations and host immune-clearance. We herein develop an alternative transplantation strategy with the aid of a microfluidic-templating microgel cell carrier to achieve substantially enhanced loading and delivery efficiency of hESC-RPE cells, thereby promoting visual function recovery after subretinal injection in the RP model Royal College of Surgeons (RCS) rats. Specifically, injectable monodispersed microgels consisting of gelatin-methacryloyl/Hyaluronic acid-methacryloyl core coated with fibrin shell (denoted as Fib@GHMS) were fabricated in a high-throughput and controllable manner, facilitating the adhesion and proliferation of hESC-RPE cells. RCS rats treated with microcarriers showed significantly improved visual function, evidenced by increased B-wave amplitudes and the preservation of the inner nuclear layer at 8 weeks post-surgery. In conclusion, our innovative delivery system Fib@GHMS for hESC-RPE cell transplantation presents a potential therapeutic graft for retinal tissue engineering. It may open a new avenue for clinical transplantation of minimally invasive cell-based treatments in retinal degenerative diseases.
视网膜色素上皮（RPE）细胞是对视觉至关重要的特殊神经细胞，而人胚胎干细胞衍生的视网膜色素上皮（hESC-RPE）细胞作为治疗视网膜色素变性（RP）等视网膜退行性疾病的可行细胞来源具有巨大潜力。然而，由于操作过程中有害的剪切力和宿主免疫清除作用，hESC-RPE细胞悬液的移植效率和存活率相对较低。我们在此借助微流控模板微凝胶细胞载体开发了一种替代移植策略，以显著提高hESC-RPE细胞的负载和递送效率，从而促进皇家外科学院（RCS）大鼠RP模型视网膜下注射后视觉功能的恢复。具体而言，以高通量和可控的方式制备了由明胶-甲基丙烯酰/透明质酸-甲基丙烯酰核心包裹纤维蛋白壳组成的可注射单分散微凝胶（记为Fib@GHMS），促进了hESC-RPE细胞的黏附和增殖。用微载体治疗的RCS大鼠视觉功能显著改善，术后8周B波振幅增加和内核层保留证明了这一点。总之，我们用于hESC-RPE细胞移植的创新递送系统Fib@GHMS为视网膜组织工程提供了一种潜在的治疗移植物。它可能为视网膜退行性疾病基于细胞的微创治疗的临床移植开辟一条新途径。
