Successful Application of Ex Vivo Expanded Human Autologous Oral Mucosal Epithelium for the Treatment of Total Bilateral Limbal Stem Cell Deficiency

Authors

  • Sai Kolli,

    1. Institute of Genetic Medicine, Newcastle University, Newcastle, United Kingdom
    2. Department of Ophthalmology, Royal Victoria Infirmary, Newcastle University, Newcastle, United Kingdom
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  • Sajjad Ahmad,

    1. Institute of Genetic Medicine, Newcastle University, Newcastle, United Kingdom
    2. Department of Ophthalmology, Royal Victoria Infirmary, Newcastle University, Newcastle, United Kingdom
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  • Hardeep Singh Mudhar,

    1. National Specialist Ophthalmic Pathology Service Laboratory (NSOPS), Department of Histopathology, Royal Hallamshire Hospital, Sheffield, United Kingdom
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  • Adam Meeny,

    1. National Specialist Ophthalmic Pathology Service Laboratory (NSOPS), Department of Histopathology, Royal Hallamshire Hospital, Sheffield, United Kingdom
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  • Majlinda Lako,

    Corresponding author
    1. Institute of Genetic Medicine, Newcastle University, Newcastle, United Kingdom
    • Correspondence: Majlinda Lako, Ph.D., Newcastle University, Institute of Genetic Medicine, International Centre for Life, Central Parkway, Newcastle upon Tyne NE1 3BZ, U.K. Telephone: 44-191-241-8688; Fax: 44-191-241-8666; e-mail: Majlinda.Lako@ncl.ac.uk

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  • Francisco C. Figueiredo

    1. Institute of Genetic Medicine, Newcastle University, Newcastle, United Kingdom
    2. Department of Ophthalmology, Royal Victoria Infirmary, Newcastle University, Newcastle, United Kingdom
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Abstract

Ocular surface reconstruction with ex vivo expanded limbal stem cells (LSCs) is a widely used clinical treatment for patients with limbal stem cell deficiency (LSCD). This is not applicable to patients with bilateral LSCD where there are no remaining LSCs. Cultivated oral mucosa epithelium (OME) has been used as an alternative source of autologous epithelial stem cells for ocular reconstruction in few clinical trials. However, successful generation of stratified OME epithelium has only been achieved in the presence of animal feeder cells and/or animal-derived products in the culture media, likely to contribute to increased risk of pathogen transmission and graft rejection. In this study, we report generation of multilayered OME epithelium that shares many of the characteristics of corneal epithelium using a fully compliant good manufacturing practice, feeder- and animal product-free method. Proof of concept was achieved by transplantation of autologous ex vivo expanded OME in two patients with histologically confirmed bilateral total LSCD that resulted in successful reversal of LSCD in the treated eye up to 24 months. Stem Cells 2014;32:2135–2146