Subretinal adipose tissue-derived mesenchymal stem cell implantation in advanced stage retinitis pigmentosa: a phase I clinical safety study

Abstract

BackgroundThis prospective clinical case series aimed to investigate the safety of subretinal adipose tissue-derived mesenchymal stem cell (ADMSC) implantation in advanced stage retinitis pigmentosa (RP).MethodsThis study included 11 patients with end-stage RP who received subretinal implantation of ADMSCs. All patients had a total visual field defect and five of them only had light perception. The best corrected visual acuity (BCVA) in the study was 20/2000. All patients had undetectable electroretinography (ERG). The worst eye of the patient was operated on and, after total vitrectomy with a 23 gauge, ADMSCs were injected subretinally. Patients were evaluated at day 1, at weeks 1–4, and then once a month for 6 months, postoperatively. BCVA, anterior segment and fundus examination, color photography, and optical coherence tomography (OCT) were carried out at each visit. Fundus fluorescein angiography (FFA), perimetry, and ERG recordings were performed before treatment and at the end of month 6, and anytime if necessary during the follow-up.ResultsAll 11 patients completed the 6-month follow-up. None of them had systemic complications. Five patients had no ocular complications. One of the patients experienced choroidal neovascular membrane (CNM) at the implantation site and received an intravitreal anti-vascular endothelial growth factor drug once. Five patients had epiretinal membrane around the transplantation area and at the periphery, and received a second vitrectomy and silicon oil injection. There was no statistically significant difference in BCVA and ERG recordings from baseline. Only one patient experienced an improvement in visual acuity (from 20/2000 to 20/200), visual field, and ERG. Three patients mentioned that the light and some colors were brighter than before and there was a slight improvement in BCVA. The remaining seven patients had no BCVA improvement (five of them only had light perception before surgery).ConclusionsStem cell treatment with subretinal implantation of ADMSCs seems to have some ocular complications and should be applied with caution. The results of this study provide the first evidence of the short-term safety of ADMSCs in humans, and clarifies the complications of the therapy which would be beneficial for future studies. To optimize the cell delivery technique and to evaluate the effects of this therapy on visual acuity and the quality of life of these patients, future studies with a larger number of cases will be necessary.

Concise Review: A Safety Assessment of Adipose-Derived Cell Therapy in Clinical Trials: A Systematic Review of Reported Adverse Events

“…Almost all organ system have been implicated in adipose‐derived cell therapy. The indication for treatment in the included studies was (in order count) soft tissue , gastrointestinal , musculoskeletal , rheumatological , ulcer/ischemic limb , urogenital , cardiac , neurological , immunological , pulmonary , and ophthalmological (Fig. A).…”

Management of retinitis pigmentosa by Wharton’s jelly derived mesenchymal stem cells: preliminary clinical results

“…In intravitreal and subretinal applications, severe complications have been reported which include proliferative vitreoretinal bands, tractional retinal detachment, exudative retinal detachment etc. [41,[47][48][49][50][51]. Suprachoroidal, subtenon or peribulbar administration methods are not X, mean values obtained from 34 eyes (32 patients); SD standard deviation; %95 CI L and U, 95% confidence interval of the difference (mean) *Bold: Significant p values and related data (i.e., coefficient and standard error) are set in italics Fig.…”

Suprachoroidal Adipose Tissue-Derived Mesenchymal Stem Cell Implantation in Patients with Dry-Type Age-Related Macular Degeneration and Stargardt's Macular Dystrophy: 6-Month Follow-Up Results of a Phase 2 Study

“…Isolation and culture of ADMSCs and their flow cytometry analyses were performed as previously mentioned by our study group (Oner et al, 2016).…”

“…In the previous study of ours where we performed subretinal ADMSC implantation in advanced-stage patients with RP, we faced various ocular complications, including choroidal neovascular membrane at the site of the implantation and epiretinal membrane around the transplantation site and at the periphery, causing localized peripheral tractional retinal detachment, which needed second surgeries, including vitrectomy and silicon oil injections, and led us to the need for modifying the initial technique (Oner et al, 2016;Oner and Sevim, 2017;Oner, 2018). The suprachoroidal…”