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• W60392192 abstract "Adult stem cells are cells with a high capacity for self-renewal that can produce terminally differentiated progeny. Stem cells generate an intermediate population of committed progenitors, often referred to as transit amplifying (TA) cells, that terminally differentiate after a limited number of cell divisions. Human keratinocyte stem cells are clonogenic and are known as holoclones. Human corneal stem cells are segregated in the limbus while limbal-derived TA cells form the corneal epithelium. Self-renewal and proliferation and deifferentiation of limbal stem cells are regulated by the ΔNp63 (α,β and γ), C/EBPδ and Bmi1 transcription factors. Cultivated limbal stem cells generate sheets of corneal epithelium suitable for clinical application. We report long-term (up to 10 years) clinical results obtained in an homogeneous group of 112 patients presenting with corneal opacification and visual loss due to chemical burn-dependent limbal stem cell deficiency. The corneal epithelium and the visual acuity of these patients have been restored by grafts of autologous cultured limbal keratinocytes. Clinical results were assessed by Kaplan-Meyer, Chi-square, Mann Whitney, Mc-Nemar and Kruskal-Wallis statistical analyses. Mutations in genes encoding the basement membrane component laminin 5 (LAM5) cause junctional epidermolysis bullosa (JEB), a devastating and often fatal skin adhesion disorder. Epidermal stem cells from an adult patient affected by LAM5-β3-deficient JEB were transduced with a retroviral vector expressing the β3 cDNA and used to prepare genetically corrected cultured epidermal grafts. Nine grafts were transplanted onto surgically prepared regions of the patient's legs. Engraftment was complete after 8 days. Synthesis and proper assembly of normal levels of functional LAM5 was observed, together with the development of a firmly adherent epidermis that remained stable for the duration of the follow-up (3.5 years) in the absence of blisters, infections, inflammation or immune response. Proviral integration site analysis indicated that the regenerated epidermis is maintained by a defined repertoire of transduced stem cells. These data show that ex vivo gene therapy of JEB is feasible and leads to full functional correction of the disease." @default.
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• W60392192 date "2010-04-01" @default.
• W60392192 modified "2023-09-23" @default.
• W60392192 title "Human epithelial stem cells in corneal regeneration and epidermal gene therapy" @default.
• W60392192 doi "https://doi.org/10.1096/fasebj.24.1_supplement.64.4" @default.
• W60392192 hasPublicationYear "2010" @default.
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