Phase 1 clinical study of an embryonic stem cell–derived retinal pigment epithelium patch in age-related macular degeneration

• Published in: Nature biotechnology Vol. 36; no. 4; pp. 328 - 337
• Main Authors: da Cruz, Lyndon, Fynes, Kate, Georgiadis, Odysseas, Kerby, Julie, Luo, Yvonne H, Ahmado, Ahmad, Vernon, Amanda, Daniels, Julie T, Nommiste, Britta, Hasan, Shazeen M, Gooljar, Sakina B, Carr, Amanda-Jayne F, Vugler, Anthony, Ramsden, Conor M, Bictash, Magda, Fenster, Mike, Steer, Juliette, Harbinson, Tricia, Wilbrey, Anna, Tufail, Adnan, Feng, Gang, Whitlock, Mark, Robson, Anthony G, Holder, Graham E, Sagoo, Mandeep S, Loudon, Peter T, Whiting, Paul, Coffey, Peter J
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01.04.2018; Nature Publishing Group
• Subjects: 13; 13/1; 14; 14/63; 59; 631/61/490; 692/308/2171; Acuity; Age; Age related diseases; Aged; Agriculture; Animals; Basement Membrane - diagnostic imaging; Basement Membrane - growth & development; Bioinformatics; Biomedical Engineering/Biotechnology; Biomedicine; Biotechnology; Blindness; Care and treatment; Cell Differentiation - genetics; Embryonic stem cells; Epithelium; Feasibility studies; Female; Health aspects; Human Embryonic Stem Cells - transplantation; Humans; Immunosuppression; Life Sciences; Macular degeneration; Macular Degeneration - diagnostic imaging; Macular Degeneration - pathology; Macular Degeneration - therapy; Male; Methods; Mice; Middle Aged; Optical Coherence Tomography; Patients; Retina; Retinal pigment epithelium; Retinal Pigment Epithelium - diagnostic imaging; Retinal Pigment Epithelium - growth & development; Retinal Pigment Epithelium - transplantation; Safety; Stem cell transplantation; Stem Cell Transplantation - adverse effects; Stem cells; Surgical instruments; Swine; Tomography, Optical Coherence; Transplantation; Tumorigenicity; Visual acuity; Visual Acuity - physiology
• ISSN: 1087-0156; 1546-1696; 1546-1696
• DOI: 10.1038/nbt.4114

An engineered patch of retinal pigment epithelium generated from human embryonic stem cells is transplanted into the eyes of two patients. Age-related macular degeneration (AMD) remains a major cause of blindness, with dysfunction and loss of retinal pigment epithelium (RPE) central to disease progression. We engineered an RPE patch comprising a fully differentiated, human embryonic stem cell (hESC)–derived RPE monolayer on a coated, synthetic basement membrane. We delivered the patch, using a purpose-designed microsurgical tool, into the subretinal space of one eye in each of two patients with severe exudative AMD. Primary endpoints were incidence and severity of adverse events and proportion of subjects with improved best-corrected visual acuity of 15 letters or more. We report successful delivery and survival of the RPE patch by biomicroscopy and optical coherence tomography, and a visual acuity gain of 29 and 21 letters in the two patients, respectively, over 12 months. Only local immunosuppression was used long-term. We also present the preclinical surgical, cell safety and tumorigenicity studies leading to trial approval. This work supports the feasibility and safety of hESC-RPE patch transplantation as a regenerative strategy for AMD.