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The central nervous system is composed of the brain and the spinal cord. The brain is a complex organ that processes and coordinates activities of the body in bilaterian, higher-order animals. The development of the brain mirrors its complex function as it requires intricate genetic signalling at specific times, and deviations from this can lead to brain(More)
Preclinical development of human cells for potential therapeutic application in neurodegenerative diseases requires that their long-term survival, stability and functional efficacy be studied in animal models of human disease. Here we describe a strategy for long-term immune protection of human fetal and stem cell-derived neural cells transplanted into the(More)
Neural transplantation as a therapeutic strategy in neurodegenerative disorders offers to replace cells lost during the disease process, with the potential to reconstruct dysfunctional circuitry, thus alleviating associated disease symptoms. The focal loss of striatal cells, specifically medium-sized spiny neurons (MSN) in Huntington's disease (HD), makes(More)
Human donor cells, including neurally directed embryonic stem cells and induced pluripotent stem cells with the potential to be used for neural transplantation in a range of neurodegenerative disorders, must first be tested preclinically in rodent models of disease to demonstrate safety and efficacy. One strategy for circumventing the rejection of(More)
Reconstruction of CNS circuitry is a major aim of neural transplantation, and is currently being assessed clinically using foetal striatal tissue in Huntington's disease. Recent work suggests that neuronal precursors derived from foetal striatum may have a greater capacity than primary foetal striatum to project to the usual striatal target areas such as(More)
We previously reported that early passage human foetal neural progenitors (hFNPs) survive long-term in the rodent host brain whereas late passage cells disappear at later post-graft survival times. The extent to which this finding is related to changes in the expanded FNPs or in the adult host brain environment was not determined. Here we report the effect(More)
The efficient generation of striatal neurons from human embryonic stem cells (hESCs) and induced pluripotent stem cells (hiPSCs) is fundamental for realising their promise in disease modelling, pharmaceutical drug screening and cell therapy for Huntington's disease. GABAergic medium-sized spiny neurons (MSNs) are the principal projection neurons of the(More)
"Proof-of-principle" that cell replacement therapy works for neurodegeneration has been reported, but only using donor cells collected from fetal brain tissue obtained from surgical terminations of pregnancy. Surgical terminations of pregnancy represent an increasingly limited supply of donor cells due to the tendency towards performing medical termination(More)
Ketamine alone or supplemented by diazepam or xylazine has been used and evaluated as an anaesthetic in a range of animals including snakes, tortoises, lizards, birds, ferrets, dogs, cats, pigs, sheep, goats, non-human primates, rabbits, guinea pigs, rats, mice and hamsters. Ketamine alone has severe limitations in most species, but in combination has(More)
A short period of daily treatment with cyclosporin A (25 mg/kg orally or 18 mg/kg by intramuscular injection) induced specific tolerance lasting more than 12 months in 60% of nephrectomised rabbits allografted with one kidney. Tolerant rabbits accepted second kidney and skin allografts from the original donor even though all immunosuppressive therapy had(More)