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.

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We acknowledge H. Moore, Stem Cell Derivation Facility, Centre for Stem Cell Biology (CSCB), University of Sheffield for derivation of the original SHEF-1 hESC line and P. Keane and M. Cheetham for comments on the paper. We thank R. McKernan for support and input throughout the project. L.d.C. and P.J.C. received the following grants and donations and would like to acknowledge that they were used to fund the studies reported in this article: Anonymous Donor, USA, Establishment of The London Project to Cure Blindness - Donation. Lincy Foundation, USA, The London Project To Cure Blindness: Funding Towards The Production Of A Cell Based Therapy For Late Stage Age-Related Macular Degeneration - P12761. Macular Disease Society Studentship – Donation. MRC, Stem Cell Based Treatment Strategy For Age-Related Macular Degeneration (AMD) - G1000730. CIRM (California Institute of Regenerative Medicine) LA1_C2-02086. Pfizer Inc, The Development Plan For A Phase I/IIa Clinical Trial Implanting HESC Derived RPE for AMD - PF-05406388. Moorfields Biomedical Research Centre, National Institute for Health Research (NIHR) - BRC2_011. The Michael Uren Foundation R170010A.

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  1. The London Project to Cure Blindness, ORBIT, Institute of Ophthalmology, University College London (UCL), London, UK.

    • Lyndon da Cruz
    • , Kate Fynes
    • , Odysseas Georgiadis
    • , Yvonne H Luo
    • , Ahmad Ahmado
    • , Britta Nommiste
    • , Shazeen M Hasan
    • , Sakina B Gooljar
    • , Amanda-Jayne F Carr
    • , Anthony Vugler
    • , Conor M Ramsden
    •  & Peter J Coffey
  2. NIHR Biomedical Research Centre at Moorfields Eye Hospital NHS Foundation Trust, UCL Institute of Ophthalmology, London, UK.

    • Lyndon da Cruz
    • , Odysseas Georgiadis
    • , Yvonne H Luo
    • , Adnan Tufail
    • , Anthony G Robson
    • , Graham E Holder
    • , Mandeep S Sagoo
    •  & Peter J Coffey
  3. Moorfields Eye Hospital NHS Foundation Trust, London, UK.

    • Lyndon da Cruz
    • , Odysseas Georgiadis
    • , Yvonne H Luo
    • , Conor M Ramsden
    • , Adnan Tufail
    • , Anthony G Robson
    • , Graham E Holder
    •  & Mandeep S Sagoo
  4. Wellcome/EPSRC Centre for Interventional & Surgical Sciences (WEISS), Charles Bell House, London, UK.

    • Lyndon da Cruz
  5. Pfizer, Granta Park, Cambridge, UK.

    • Julie Kerby
    • , Magda Bictash
    • , Mike Fenster
    • , Juliette Steer
    • , Tricia Harbinson
    • , Anna Wilbrey
    • , Gang Feng
    • , Mark Whitlock
    • , Peter T Loudon
    •  & Paul Whiting
  6. Cell and Gene Therapy Catapult, London, UK.

    • Julie Kerby
  7. Cells for Sight, Transplantation & Research Program, UCL Institute of Ophthalmology, London, UK.

    • Amanda Vernon
    •  & Julie T Daniels
  8. UCL Institute of Neurology, Queen Square, London, UK.

    • Paul Whiting
  9. Center for Stem Cell Biology and Engineering, NRI, UC, Santa Barbara, California, USA.

    • Peter J Coffey


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L.d.C., P.T.L., P.W., and P.J.C. designed all of the animal studies and the clinical study, developed the methodology for these studies, collected the data, performed the analysis, and wrote the manuscript. L.d.C. performed the pig and human surgery. K.F., J.K., A.A., A.Ve., J.T.D., B.N., S.M.H., S.B.G., A.-J.F.C., A.Vu., C.M.R., M.B., M.F., J.S., T.H., and A.W. developed, isolated, and prepared the hESC-RPE and performed the engineering of the hESC-RPE patch; and assisted in designing and conducting the mouse and pig studies, collecting the data, performing the analysis, and writing the manuscript. A.A. and A.Vu. performed the mouse surgery. O.G., Y.H.L., A.A., A.T., G.F., M.W., A.G.R., G.E.H. and M.S.S. assisted in designing the clinical study, developing the methodology, collecting the data, performing the analysis, and writing the manuscript.

Competing interests

J.K., M.B., M.F., J.S., T.H., G.F., M.W., P.T.L., and P.W. were all employees of Pfizer during the period of this clinical trial. This study was sponsored by Pfizer Inc. L.d.C. and P.J.C. are named on two patents lodged by University College London Business. They are Patent Application No. PCT/GB2009/000917 (for the patch) and International Patent Application No. PCT/GB2011/051262 (for the surgical tool).

Corresponding author

Correspondence to Lyndon da Cruz.

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