Abstract
BackgroundRetinitis pigmentosa is a common genetic disease that causes retinal degeneration and blindness for which there is currently no curable treatment available. Vision preservation was observed in retinitis pigmentosa animal models after retinal stem cell transplantation. However, long-term safety studies and visual assessment have not been thoroughly tested in retinitis pigmentosa patients.MethodsIn our pre-clinical study, purified human fetal-derived retinal progenitor cells (RPCs) were transplanted into the diseased retina of Royal College of Surgeons (RCS) rats, a model of retinal degeneration. Based on these results, we conducted a phase I clinical trial to establish the safety and tolerability of transplantation of RPCs in eight patients with advanced retinitis pigmentosa. Patients were studied for 24 months.ResultsAfter RPC transplantation in RCS rats, we observed moderate recovery of vision and maintenance of the outer nuclear layer thickness. Most importantly, we did not find tumor formation or immune rejection. In the retinis pigmentosa patients given RPC injections, we also did not observe immunological rejection or tumorigenesis when immunosuppressive agents were not administered. We observed a significant improvement in visual acuity (P < 0.05) in five patients and an increase in retinal sensitivity of pupillary responses in three of the eight patients between 2 and 6 months after the transplant, but this improvement did not appear by 12 months.ConclusionOur study for the first time confirmed the long-term safety and feasibility of vision repair by stem cell therapy in patients blinded by retinitis pigmentosa.Trial registrationWHO Trial Registration, ChiCTR-TNRC-08000193. Retrospectively registered on 5 December 2008.
Highlights
Retinitis pigmentosa is a common genetic disease that causes retinal degeneration and blindness for which there is currently no curable treatment available
We describe the preparation and isolation of highly enriched human retinal progenitor cells (RPCs) derived from early developmental fetuses and investigated the potential of these cells to integrate into the host retinas of Royal College of Surgeons (RCS) rats and to restore a visual response
Gene expression analysis confirmed that the typical early eyecup transcription factor genes Pax6 and Six6 (Fig. 1c) increased 5–10 fold compared to that seen in human embryonic stem cell (hESC) cultures; the expression of photoreceptor precursor markers, such as recoverin and Cone-rod homeobox-containing gene (CRX), was much higher in the RPCs
Summary
Retinitis pigmentosa is a common genetic disease that causes retinal degeneration and blindness for which there is currently no curable treatment available. Vision preservation was observed in retinitis pigmentosa animal models after retinal stem cell transplantation. Studies using retinitis pigmentosa animal models indicated that the transplanted cells were able to differentiate into photoreceptors, integrate into the host retinas, and rescue vision [7,8,9,10,11]. Liu et al Stem Cell Research & Therapy (2017) 8:209 suggested that it is possible to transplant human RPCs to treat retinitis pigmentosa patients. Transplanting ESCs or iPSCs carries the potential risk of tumor formation and gene mutation [15, 16]
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