A5040956324- Pluripotent Stem Cells Research
- CRISPR and Genetic Engineering
- Nerve injury and regeneration
- Nuclear Receptors and Signaling
- Tissue Engineering and Regenerative Medicine
- Neurogenesis and neuroplasticity mechanisms
- 3D Printing in Biomedical Research
- Genetics, Aging, and Longevity in Model Organisms
- RNA Interference and Gene Delivery
- Telomeres, Telomerase, and Senescence
- Virus-based gene therapy research
Kettering University
2024
Florey Institute of Neuroscience and Mental Health
2017-2022
The University of Melbourne
2017-2022
Abstract Despite advancements in human pluripotent stem cells (hPSCs) differentiation protocols to generate appropriate neuronal progenitors suitable for transplantation Parkinson’s disease, resultant grafts contain low proportions of dopamine neurons. Added this is the tumorigenic risk associated with potential presence incompletely patterned, proliferative within grafts. Here, we utilised a hPSC line carrying FailSafe TM suicide gene (thymidine kinase linked cyclinD1) selectively ablate...
Abstract The survival and synaptic integration of transplanted dopaminergic (DA) progenitors are essential for ameliorating motor symptoms in Parkinson's disease (PD). Human pluripotent stem cell (hPSC)‐derived DA are, however, exposed to numerous stressors prior to, during, implantation that result poor survival. Additionally, hPSC‐derived grafts show inferior plasticity compared fetal tissue grafts. These observations suggest a more conducive host environment may improve graft outcomes....
Human pluripotent stem cells (hPSCs) are a promising resource for the replacement of degenerated ventral midbrain dopaminergic (vmDA) neurons in Parkinson's disease. Despite recent advances protocols vitro generation vmDA neurons, asynchronous and heterogeneous nature differentiations results transplants surprisingly low neuron purity. As field toward clinic, it will be optimal, if not essential, to remove poorly specified potentially proliferative from donor preparations ensure safety...
Midbrain dopaminergic (DA) neurons include many subtypes characterized by their location, connectivity and function. Surprisingly, mechanisms underpinning the specification of A9 [responsible for motor function, including within ventral midbrain (VM) grafts treating Parkinson9s disease (PD)] over adjacent A10, remains largely speculated. We assessed impact synaptic targeting on survival, integration, phenotype acquisition VM generated from fetal tissue or human pluripotent stem cells (PSCs)....
Human pluripotent stem cells are a valuable resource for transplantation, yet our ability to profile xenografts is largely limited low-throughput immunohistochemical analysis by difficulties in readily isolating grafts transcriptomic and/or proteomic profiling. Here, we present simple methodology utilizing differences the RNA sequence between species discriminate xenograft from host gene expression (using qPCR or sequencing [RNA-seq]). To demonstrate approach, assessed of undifferentiated...
Abstract Pluripotent stem cells (PSCs) are a valuable tool for interrogating development, disease modelling, drug discovery and transplantation. Despite the burgeoned capability to fate restrict human PSCs specific neural lineages, comparative protocols mouse have not similarly advanced. Mouse fail recapitulate consequently yielding highly heterogeneous populations, yet remain scientific as differentiation is rapid, cost effective an extensive repertoire of transgenic lines provides...
Abstract The derivation of neurotransmitter and region-specific neuronal populations from human pluripotent stem cells (PSC) provides impetus for advancing cell therapies into the clinic. At forefront is our ability to generate ventral midbrain (VM) dopaminergic (DA) progenitors, suitable transplantation in Parkinson’s disease (PD). Pre-clinical studies, however, have highlighted low proportion DA neurons within these grafts their inferior plasticity by comparison fetal donor transplants....
Tissue Programmed Hydrogels In article number 2105301, David R. Nisbet, Clare L. Parish, and co-workers show that encapsulating human stem cell-derived dopamine progenitors within a neural tissue biomimetic hydrogel enhances their engraftment in an animal model of Parkinson's disease. The laminin-based hydrogel, simultaneously sustains delivery glial neurotrophic factor increases neuron survival plasticity, consequently the functional capacity graft to reverse motor deficits.