Bahrani Fard 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
bioRxiv. 2025 Mar 26:2024.05.13.593917. doi: 10.1101/2024.05.13.593917.
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 nine months after a single dose of only 1500 magnetically-steered hAMSCs, explained by increased outflow through the conventional pathway and associated with an 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 three 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.
A novel magnetic cell therapy provided effective intraocular pressure reduction in a mouse model, motivating future translational studies.
小梁网（TM）细胞疗法已被提议作为治疗青光眼眼内压（IOP）升高的下一代疗法，青光眼是不可逆失明的最常见原因。我们利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）。单次仅注入1500个经磁引导的hAMSCs后九个月，我们观察到眼内压降低了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，且与小梁网细胞增多有关。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%，且致瘤风险增加。在两种情况下，移植后三周在虹膜角膜角仍可检测到注入的细胞。基于所输送细胞的位置，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细胞疗法在青光眼性高眼压的长期治疗中具有潜力。
一种新型磁细胞疗法在小鼠模型中有效降低了眼内压，为未来的转化研究提供了动力。
