Postnatal periodontal ligament as a novel adult stem cell source for regenerative corneal cell therapy |
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Authors: | Gary Hin‐Fai Yam Ericia Pei‐Wen Teo Melina Setiawan Matthew J Lovatt Nur Zahirah Binte M Yusoff Matthias Fuest Bee‐Tin Goh Jodhbir S Mehta |
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Affiliation: | 1. Tissue Engineering and Stem Cell Group, Singapore Eye Research Institute, Singapore;2. Ophthalmology and Visual Science Academic Clinical Research Program, Duke‐National University of Singapore Graduate Medical School, Singapore;3. Department of Ophthalmology, RWTH Aachen University, Aachen, Germany;4. Department of Oral and Maxillofacial Surgery, National Dental Centre, Singapore;5. Cornea and External Eye Disease Service Team, Singapore National Eye Centre, Singapore;6. School of Material Science and Engineering, Nanyang Technological University, Singapore |
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Abstract: | Corneal opacities are a leading cause of global blindness. They are conventionally treated by the transplantation of donor corneal tissue, which is, restricted by a worldwide donor material shortage and allograft rejection. Autologous adult stem cells with a potential to differentiate into corneal stromal keratocytes (CSKs) could offer a suitable choice of cells for regenerative cell therapy. Postnatal periodontal ligament (PDL) contains a population of adult stem cells, which has a similar embryological origin as CSK, that is cranial neural crest. We harvested PDL cells from young adult teeth extracted because of non‐functional or orthodontic reason and differentiated them towards CSK phenotype using a two‐step protocol with spheroid formation followed by growth factor and cytokine induction in a stromal environment (human amnion stroma and porcine corneal stroma). Our results showed that the PDL‐differentiated CSK‐like cells expressed CSK markers (CD34, ALDH3A1, keratocan, lumican, CHST6, B3GNT7 and Col8A2) and had minimal expression of genes related to fibrosis and other lineages (vasculogenesis, adipogenesis, myogenesis, epitheliogenesis, neurogenesis and hematogenesis). Introduction of PDL spheroids into the stroma of porcine corneas resulted in extensive migration of cells inside the host stroma after 14‐day organ culture. Their quiescent nature and uniform cell distribution resembled to that of mature CSKs inside the native stroma. Our results demonstrated the potential translation of PDL cells for regenerative corneal cell therapy for corneal opacities. |
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Keywords: | cornea corneal stromal keratocytes differentiation periodontal ligament stem cells |
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