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J.T. Daniels, A.J. Shortt, G.A. Secker, J.K. Dart, P.T. Khaw, S.J. Tuft; Production, Transplantation and Outcome of Good Manufacturing Practice Compliant Limbal Epithelial Stem Cell Therapy . Invest. Ophthalmol. Vis. Sci. 2006;47(13):3015.
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To report the treatment of patients with corneal stem cell failure using limbal epithelial stem cells (LESC) cultured with Good Manufacturing Practice (GMP) and UK Department of Health Tissue Banking Accreditation.
LESC harvested from autologous limbal biopsies or cadaveric human corneas were cultured on human amniotic membrane. All donors were serologically screened for transmissible diseases. Culture procedures were validated and conducted in a class 100 cleanroom with GMP. All animal–derived cell culture products were fully traceable. Following administration of immunusuppression (for allograft recipients) and preparation of the recipient’s cornea cultured LESC were transplanted onto the ocular surface and monitored over time.
The Cells for Sight Transplantation and Research Programme attained Tissue Banking GMP accreditation in April 2005. Successful culture and transplantation of LESC cultured under GMP has been achieved in 6 patients (2 autografts and 4 allografts) so far. Analysis of cultured grafts revealed that a LESC phenotype could be maintained despite cell culture modifications required for GMP compliance. One patient developed an unrelated surgical complication and required a second graft. A stable epithelium and improvement in the clinical parameters of stem cell deficiency was observed in 5 out of 6 patients. Improvement in visual acuity has been observed in 2 patients to date. In the remaining patients improvement in visual acuity has been delayed by opacity of the amnion and other ocular abnormalities.
Transplantation of cultured LESC is a novel therapy at the proof of concept stage. Our early data suggests that this treatment can be successfully used to treat patients with long standing corneal stem cell deficiency. GMP compliance throughout all aspects of therapy production reduces the risk of transmission of human and animal–derived infectious agents, provides a full audit trail and ensures that all tissue are procured and processed in an ethical and quality assured manner. Whilst an onerous task, it is possible to successfully culture LESC for patient transplantation in accordance with GMP regulatory requirements. To our knowledge this is the first LESC therapy study reported to be conducted under GMP.
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