本文章介绍了土耳其安卡拉大学眼科医院在2019年4月至2019年10月用脐带间充质干细胞针对视网膜色素变性进行的第三期临床试验
32位RP患者（34只眼）纳入研究，Tenon氏囊下注入间充质干细胞，治疗6个月后视力提高10.1个字母数，视野改善，外层视网膜厚度增加，多焦视网膜电图幅值增加，视网膜电图潜时缩短，未出现任何眼部和全身不良事件，证实Tenon氏囊下注射治疗RP是安全有效的。
Management of retinitis pigmentosa by
Wharton’s jelly derived mesenchymal stem
cells: preliminary clinical results
Emin ÖZMERT1 and Umut ARSLAN2*
Abstract
Purpose: The aim of this study is to determine if umbilical cord Wharton’s jelly derived mesenchymal stem cells
implanted in sub-tenon space have beneficial effects on visual functions in retinitis pigmentosa patients by
reactivating the degenerated photoreceptors in dormant phase.
Material and methods: This prospective, open-label, phase-3 clinical trial was conducted between April of 2019 and
October of 2019 at Ankara University Faculty of Medicine, Department of Ophthalmology. 32 RP patients (34 eyes)
were included in the study. The patients were followed for 6 months after the Wharton’s jelly derived mesenchymal
stem cell administration, and evaluated with consecutive examinations. All patients underwent a complete routine
ophthalmic examination, and best corrected visual acuity, optical coherens tomography angiography, visual field,
multifocal and full-field electroretinography were performed. The quantitative results were obtained from a comparison
of the pre-injection and final examination (6th month) values.
Results: The mean best corrected visual acuity was 70.5 letters prior to Wharton’s jelly derived mesenchymal stem cell
application and 80.6 letters at the 6th month (p = 0.01). The mean visual field median deviation value was 27.3 dB
before the treatment and 24.7 dB at the 6th month (p = 0.01). The mean outer retinal thickness was 100.3 μm before
the treatment and 119.1 μm at 6th month (p = 0.01). In the multifocal electroretinography results, P1 amplitudes
improved in ring1 from 24.8 to 39.8 nv/deg2 (p = 0.01), in ring2 from 6.8 to 13.6 nv/deg2 (p = 0.01), and in ring3 from
3.1 to 5.7 nv/deg2 (p = 0.02). P1 implicit times improved in ring1 from 44.2 to 32.4 ms (p = 0.01), in ring2 from 45.2 to
33.2 ms (p = 0.02), and in ring3 from 41.9 to 32.4 ms (p = 0.01). The mean amplitude improved in 16 Tds from 2.4 to 5.0
nv/deg2 (p = 0.01) and in 32 Tds from 2.4 to 4.8 nv/deg2 (p = 0.01) in the full-field flicker electroretinography results.
Full field flicker electroretinography mean implicit time also improved in 16 Tds from 43.3 to 37.9 ms (p = 0.01). No
ocular or systemic adverse events related to the two types of surgical methods and/or Wharton’s jelly derived
mesenchymal stem cells itself were observed during the follow-up period.
Conclusion: RP is a genetic disorder that can result in blindness with outer retinal degeneration. Regardless of the type of
genetic mutation, sub-tenon Wharton’s jelly derived mesenchymal stem cell administration appears to be an effective and
safe option. There are no serious adverse events or ophthalmic / systemic side effects for 6 months follow-up. Although the
long-term adverse effects are still unknown, as an extraocular approach, subtenon implantation of the stem cells seems to
be a reasonable way to avoid the devastating side effects of intravitreal/submacular injection. Further studies that include
long-term follow-up are needed to determine the duration of efficacy and the frequency of application.
Trial registration: SHGM56733164. Redistered 28 January 2019 https://shgm.saglik.gov.tr/organ-ve-doku-naklikoordinatorlugu/56733164/203 E.507.
Keywords: Retinitis pigmentosa, Stem cell, Wharton’s jelly derived mesenchymal stem cell, Umbilical cord stem cell, Subtenon space |
