Woodruff School of Mechanical Engineering, Georgia Institute of Technology, Atlanta, GA, USA.
School of Chemistry and Biochemistry, Georgia Institute of Technology, Atlanta, GA, USA.
Exp Eye Res. 2023 Sep;234:109602. doi: 10.1016/j.exer.2023.109602. Epub 2023 Jul 22.
Glaucoma is the leading cause of irreversible blindness worldwide and its most prevalent subtype is primary open angle glaucoma (POAG). One pathological change in POAG is loss of cells in the trabecular meshwork (TM), which is thought to contribute to ocular hypertension and has thus motivated development of cell-based therapies to refunctionalize the TM. TM cell therapy has shown promise in intraocular pressure (IOP) control, but existing cell delivery techniques suffer from poor delivery efficiency. We employed a novel magnetic delivery technique to reduce the unwanted side effects of off-target cell delivery. Mesenchymal stem cells (MSCs) were labeled with superparamagnetic iron oxide nanoparticles (SPIONs) and after intracameral injection were magnetically steered towards the TM using a focused magnetic apparatus ("point magnet"). This technique delivered the cells significantly closer to the TM at higher quantities and with more circumferential uniformity compared to either unlabeled cells or those delivered using a "ring magnet" technique. We conclude that our point magnet cell delivery technique can improve the efficiency of TM cell therapy and in doing so, potentially increase the therapeutic benefits and lower the risk of complications such as tumorigenicity and immunogenicity.
青光眼是全球导致不可逆性失明的主要原因,其最常见的亚型是原发性开角型青光眼(POAG)。POAG 的一种病理变化是小梁网(TM)细胞的丧失,这被认为是导致眼内压升高的原因,因此激发了基于细胞的疗法来使 TM 重新发挥功能。TM 细胞疗法在控制眼内压(IOP)方面显示出了前景,但现有的细胞输送技术存在输送效率差的问题。我们采用了一种新颖的磁输送技术来减少非目标细胞输送的不良副作用。间充质干细胞(MSCs)被超顺磁氧化铁纳米颗粒(SPIONs)标记,然后通过房水内注射,使用聚焦磁设备(“点磁体”)将细胞磁性引导至 TM。与未标记的细胞或使用“环磁体”技术输送的细胞相比,这种技术能以更高的数量和更均匀的圆周度将细胞输送到 TM 附近。我们得出结论,我们的点磁体细胞输送技术可以提高 TM 细胞疗法的效率,从而可能增加治疗效果,并降低肿瘤形成和免疫原性等并发症的风险。