Bahranifard M Reza, Chan Jessica, Read A Thomas, Li Guorong, Cheng Lin, Safa Babak N, Siadat Seyed Mohammad, Jhunjhunwala Anamik, Grossniklaus Hans E, Emelianov Stanislav Y, Stamer W Daniel, Kuehn Markus H, Ethier C Ross
Woodruff School of Mechanical Engineering, Georgia Institute of Technology, Atlanta, United States.
School of Chemistry and Biochemistry, Georgia Institute of Technology, Atlanta, United States.
Elife. 2025 Jul 7;13:RP103256. doi: 10.7554/eLife.103256.
Trabecular meshwork (TM) cell therapy has been proposed as a next-generation treatment for elevated intraocular pressure (IOP) in glaucoma, the most common cause of irreversible blindness. Using a magnetic cell steering technique with excellent efficiency and tissue-specific targeting, we delivered two types of cells into a mouse model of glaucoma: either human adipose-derived mesenchymal stem cells (hAMSCs) or induced pluripotent cell derivatives (iPSC-TM cells). We observed a 4.5 [3.1, 6.0] mmHg or 27% reduction in intraocular pressure (IOP) for 9 months after a single dose of only 1500 magnetically steered hAMSCs, explained by increased outflow through the conventional pathway and associated with a higher TM cellularity. iPSC-TM cells were also effective, but less so, showing only a 1.9 [0.4, 3.3] mmHg or 13% IOP reduction and increased risk of tumorigenicity. In both cases, injected cells remained detectable in the iridocorneal angle 3 weeks post-transplantation. Based on the locations of the delivered cells, the mechanism of IOP lowering is most likely paracrine signaling. We conclude that magnetically steered hAMSC cell therapy has potential for long-term treatment of ocular hypertension in glaucoma.
小梁网（TM）细胞疗法已被提议作为青光眼眼内压（IOP）升高的下一代治疗方法，青光眼是不可逆失明的最常见原因。我们使用具有卓越效率和组织特异性靶向性的磁细胞引导技术，将两种类型的细胞导入青光眼小鼠模型：人脂肪来源的间充质干细胞（hAMSCs）或诱导多能细胞衍生物（iPSC-TM细胞）。单次仅注射1500个经磁引导的hAMSCs后，我们观察到眼内压在9个月内降低了4.5[3.1, 6.0] mmHg，即降低了27%，这是由于通过传统途径的房水流出增加所致，并且与小梁网细胞数量增加有关。iPSC-TM细胞也有效，但效果较差，仅使眼内压降低了1.9[0.4, 3.3] mmHg，即降低了13%，并且致瘤风险增加。在两种情况下，移植后3周在虹膜角膜角仍可检测到注射的细胞。基于所递送细胞的位置，降低眼内压的机制很可能是旁分泌信号传导。我们得出结论，磁引导的hAMSC细胞疗法具有长期治疗青光眼性高眼压的潜力。
