University:
Western Sydney University
Course:
MEDI 2003 | Clinical Sciences 2
Academic year:

2024
Views:

399

Pages:

3
Author:

Mariam A.

Retinal disease      Severity: o Low vision: ~2.5 million globally, ~125, 000 Australians. o Blind: ~2 million globally, ~25, 000 Australians. Tissue-specific retinal stem cells is poorly understood and require much more research before using these stem cells for treatment. Currently produce cells: o Retinal pigment epithelium (RPE). o Photoreceptors. o Muller cells. In UWS, macular degeneration research has aimed to: o Increase yield/purity of RPE production. o Establish substrates for RPE transplantation. o Understand molecular mechanisms of macular degeneration. BEST disease – a congenital form of macular degeneration. o Mutation of BEST1 gene, although genotype/phenotype correlation is imperfect (not completely penetrative). o Disease mechanism is unclear, but BEST1 protein may regulate RPE membrane potential. o The disease is characterised by lipofuscin (end-products of oxidative damage to lipids) and fluid, which damages RPE and photoreceptors. o It has similarities with age-related macular degeneration. o Loss of visual acuity in central macular leads to blindness.      UWS has the first-ever reported human embryonic stem cells with a mutation in the BEST1 gene. o This allows the investigation of molecular biology of BEST disease. o Expanding/purifying mutant BEST1-RPE. o Compare normal vs. mutant BEST1 RPE function. Current investigations using advanced cell technology: o 2 recent FDA-approved Phase 1 clinical trials (safety, not efficacy). o 2 patients (1 macular degeneration, 1 Stargardt’s macular dystrophy) treated using RPE derived from human embryonic stem cells. Method for cell transplantation: o Differentiated MA09 human embryonic stem cells to RPE (considered a xenotransplant). o Need to check quality of RPE prior to injection (are they normal, are there any infectious agents present, are there other cells, etc.). o Solution = 150μL injection (50, 000 RPE cells) into pericentral macula. Preliminary findings, 4 months after injection showed: o No retinal detachment from injection. o No abnormal growth or tumour formation. o No apparent intraocular inflammation. o No ocular pathology induced (e.g. cataract, secondary glaucoma, pain, etc.). o Both patients show improved visual acuity (but placebo can’t be dismissed yet). Future goal is to determine: o Optimal cell dose. Challenges for ocular stem cell therapies  Research-scale technical challenges. o Economically making purified effector cells. o Tissue-specific stem cells: finding, maintaining, expanding and differentiating. o Understanding molecular mechanisms of diseases.  Moving from lab-scale to production-scale. o Do small-scale techniques work at large-scale? o Quality assessment and quality control of cells.  Overcome tissue rejection. o Are patient’s own tissue-restricted stem cells suitable? o Are patient specific ‘reprogrammed cells’ feasible (high cost, long time)?  Develop appropriate clinical transplantation protocols. o What cell type is needed? o When is the optimal time for a transplant? o How many cells are needed? o What is the best delivery method, cell suspension or adhered to a matrix?