Human embryonic stem (hES) cells provide a potentially unlimited cell source for regenerative medicine. Recently, differentiation strategies were developed to direct hES cells towards neural fates in vitro. However, the interaction of hES cell progeny with the adult brain environment remains unexplored. Here we report that hES cell-derived neural precursors differentiate into neurons, astrocytes and oligodendrocytes in the normal and lesioned brain of young adult rats and migrate extensively along white matter tracts. The differentiation and migration behavior of hES cell progeny was region specific. The hES cell-derived neural precursors integrated into the endogenous precursor pool in the subventricular zone, a site of persistent neurogenesis. Like adult neural stem cells, hES cell-derived precursors traveled along the rostral migratory stream to the olfactory bulb, where they contributed to neurogenesis. We found no evidence of cell fusion, suggesting that hES cell progeny are capable of responding appropriately to host cues in the subventricular zone.
BackgroundThe cellular basis of long term radiation damage in the brain is not fully understood.Methods and FindingsWe administered a dose of 25Gy to adult rat brains while shielding the olfactory bulbs. Quantitative analyses were serially performed on different brain regions over 15 months. Our data reveal an immediate and permanent suppression of SVZ proliferation and neurogenesis. The olfactory bulb demonstrates a transient but remarkable SVZ-independent ability for compensation and maintenance of the calretinin interneuron population. The oligodendrocyte compartment exhibits a complex pattern of limited proliferation of NG2 progenitors but steady loss of the oligodendroglial antigen O4. As of nine months post radiation, diffuse demyelination starts in all irradiated brains. Counts of capillary segments and length demonstrate significant loss one day post radiation but swift and persistent recovery of the vasculature up to 15 months post XRT. MRI imaging confirms loss of volume of the corpus callosum and early signs of demyelination at 12 months. Ultrastructural analysis demonstrates progressive degradation of myelin sheaths with axonal preservation. Areas of focal necrosis appear beyond 15 months and are preceded by widespread demyelination. Human white matter specimens obtained post-radiation confirm early loss of oligodendrocyte progenitors and delayed onset of myelin sheath fragmentation with preserved capillaries.ConclusionsThis study demonstrates that long term radiation injury is associated with irreversible damage to the neural stem cell compartment in the rodent SVZ and loss of oligodendrocyte precursor cells in both rodent and human brain. Delayed onset demyelination precedes focal necrosis and is likely due to the loss of oligodendrocyte precursors and the inability of the stem cell compartment to compensate for this loss.
Cell transplantation with embryonic stem (ES) cell progeny requires immunological compatibility with host tissue. 'Therapeutic cloning' is a strategy to overcome this limitation by generating nuclear transfer (nt)ES cells that are genetically matched to an individual. Here we establish the feasibility of treating individual mice via therapeutic cloning. Derivation of 187 ntES cell lines from 24 parkinsonian mice, dopaminergic differentiation, and transplantation into individually matched host mice showed therapeutic efficacy and lack of immunological response.
Purposes:The aim of this study was to analyse clinical data of children undergoing orthokeratology (ortho-k) and to investigate patients'/parents' perspective on ortho-k via telephone interviews. Methods: Clinical records of children undergoing ortho-k from a university optometry clinic were reviewed and the effects of ortho-k on refraction, vision and cornea were investigated. A telephone interview was conducted to solicit patients'/parents' perspective of the treatment. Results: One hundred and eight files were reviewed. Median age of the children was nine years (range six to 15); mean (ϮSD) pre-treatment refractive sphere was -3.56 Ϯ 1.49 D and the median refractive cylinder was -0.50 D (range zero to -4.25 D). Significant refractive spherical reduction (58 per cent), improvement in unaided vision and corneal topographical changes were noted after only one night of wear. No significant change in astigmatism was found. Corneal staining was the most commonly observed complication with ortho-k and more than 80 per cent of patients were advised to apply ocular lubricants to loosen the lens before lens removal. Ortho-k was mainly undertaken for myopic control and about 90 per cent of the respondents reported good/very good unaided vision after ortho-k and ranked the treatment as satisfactory or very good. Lens binding and ocular discharge were the most frequently reported problems during the treatment. Conclusion: Under close monitoring, overnight ortho-k is effective and safe for reducing low to moderate myopia and the treatment is well accepted by the children.
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