Instituto de Oftalmobiología Aplicada (IOBA), Universidad de Valladolid, Campus Miguel Delibes, Pº de Belén nº 17, 47011, Valladolid, Spain.
Centro en Red de Medicina Regenerativa y Terapia Celular de Castilla y León, Valladolid, Spain.
Stem Cell Res Ther. 2023 Sep 21;14(1):261. doi: 10.1186/s13287-023-03500-7.
An effective treatment for acute non-arteritic ischemic optic neuropathy (NA-AION) has not been known or proven yet. Previous studies have suggested a neuroprotective effect of allogeneic bone marrow-derived mesenchymal stem cells. This study aims to report the results of a clinical trial on patients with acute non-arteritic optic neuropathy (NA-AION) treated with an intravitreal injection of allogeneic bone marrow-derived mesenchymal stem cells (BM-MSCs) (MSV®).
We conducted a prospective, non-randomized, clinical phase-II study (Eudra CT number 2016-003029-40; ClinicalTrials.gov Registry NCT03173638) that included 5 patients with acute unilateral NA-AION diagnosed within 2 weeks after symptom onset and who received an intravitreal injection of allogeneic BM-MSCs (0.05 ml; cell concentration: 1.5 × 10cells/mL). The patients underwent regular ophthalmological examinations and were followed for one year.
In this trial, allogeneic BM-MSCs appeared to be safe as no patients developed signs of acute nor chronic intraocular inflammation or a significant change in intraocular pressure, although an epiretinal membrane was developed in one patient. A retrolental aggregate formed shortly after the injection spontaneously disappeared within a few weeks in another phakic patient, leaving a subcapsular cataract. Visual improvement was noted in 4 patients, and amplitudes of P100 on the visually evoked potentials recordings increased in three patients. The retinal nerve fiber layer and macular ganglion cell layer thicknesses significantly decreased during the follow-up.
Besides the development of an epiretinal membrane in one patient, the intravitreal application of allogeneic BM-MSCs appeared to be intraocularly well tolerated. Consequently, not only NA-AION but also BM-MSCs deserve more clinical investigational resources and a larger randomized multicenter trial that would provide stronger evidence both about safety and the potential therapeutic efficacy of intravitreally injected allogeneic BM-MSCs in acute NA-AION.
Safety Assessment of Intravitreal Mesenchymal Stem Cells for Acute Non-Arteritic Anterior Ischemic Optic Neuropathy (NEUROSTEM). NCT03173638. Registered June 02, 2017 https://clinicaltrials.gov/ct2/show/NCT03173638 .
急性非动脉炎性前部缺血性视神经病变（NA-AION）的有效治疗方法尚未得到证实。先前的研究表明同种异体骨髓间充质干细胞具有神经保护作用。本研究旨在报告用玻璃体内注射同种异体骨髓间充质干细胞（BM-MSCs）（MSV®）治疗急性非动脉炎性前部缺血性视神经病变（NA-AION）患者的临床试验结果。
我们进行了一项前瞻性、非随机、临床二期研究（Eudra CT 编号 2016-003029-40；ClinicalTrials.gov 注册号 NCT03173638），纳入 5 例在症状出现后 2 周内诊断为单侧急性 NA-AION 的患者，并接受玻璃体内注射同种异体 BM-MSCs（0.05ml；细胞浓度：1.5×10 个细胞/ml）。所有患者均接受定期眼科检查，并随访 1 年。
在本试验中，同种异体 BM-MSCs 似乎是安全的，因为没有患者出现急性或慢性眼内炎症的迹象，也没有眼压显著变化，尽管 1 例患者出现了视网膜内膜。另一位有晶状体患者的后发性白内障在注射后不久形成的后囊下白内障在数周内自发消退。4 例患者视力改善，3 例患者视觉诱发电位记录的 P100 振幅增加。在随访期间，视网膜神经纤维层和黄斑神经节细胞层厚度显著降低。
除 1 例患者出现视网膜内膜外，玻璃体内应用同种异体 BM-MSCs 似乎耐受性良好。因此，不仅是 NA-AION，还有 BM-MSCs 都值得更多的临床研究资源和更大规模的随机多中心试验，以提供更强的证据，证明玻璃体内注射同种异体 BM-MSCs 在急性 NA-AION 中的安全性和潜在治疗效果。
急性非动脉炎性前部缺血性视神经病变的玻璃体内间充质干细胞安全性评估（NEUROSTEM）。NCT03173638。2017 年 6 月 2 日注册于 https://clinicaltrials.gov/ct2/show/NCT03173638。
