- Nerve injury and regeneration
- Tissue Engineering and Regenerative Medicine
- Pluripotent Stem Cells Research
- Electrospun Nanofibers in Biomedical Applications
- Neurogenesis and neuroplasticity mechanisms
- CRISPR and Genetic Engineering
- 3D Printing in Biomedical Research
- RNA Interference and Gene Delivery
- Supramolecular Self-Assembly in Materials
- Mesenchymal stem cell research
- Neuroscience and Neural Engineering
- Cancer, Hypoxia, and Metabolism
- Phagocytosis and Immune Regulation
- Developmental Biology and Gene Regulation
- Graphene and Nanomaterials Applications
- Nuclear Receptors and Signaling
- Fibroblast Growth Factor Research
- Virus-based gene therapy research
Florey Institute of Neuroscience and Mental Health
2017-2022
The University of Melbourne
2017-2022
Universidade Federal de São Paulo
2014-2015
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....
Abstract Improved control over spatiotemporal delivery of growth factors is needed to enhance tissue repair. Current methods are limited–requiring invasive procedures, poor targeting, and/or limited dosage and duration. Incorporation into implantable biomaterials enables stabilized avoids burst release/fluctuating doses. Here, the physical forces fibrils formed by self‐assembly epitope‐containing peptides exploited. This biomimetic hydrogel loaded with neurotrophic factor BDNF via a...
Despite heterogeneity across the six layers of mammalian cortex, all excitatory neurons are generated from a single founder population neuroepithelial stem cells. However, how these progenitors alter their layer competence over time remains unknown. Here, we used human embryonic cell-derived cortical to examine role fibroblast growth factor (FGF) and Notch signaling in influencing cell fate, assessing impact on progenitor phenotype, cell-cycle kinetics, specificity. Forced early exit, via...
Clinical studies have provided evidence for dopamine (DA) cell replacement therapy in Parkinson's Disease. However, grafts derived from foetal tissue or pluripotent stem cells (PSCs) remain heterogeneous, with a high proportion of non-dopaminergic cells, and display subthreshold reinnervation target tissues, thereby highlighting the need to identify new strategies improve graft outcomes. In recent work, Stromal Cell-Derived Factor-1 (SDF1), secreted meninges, has been shown exert many roles...
Abnormal development of ventral midbrain (VM) dopaminergic (DA) pathways, essential for motor and cognitive function, may underpin a number neurological disorders thereby highlight the importance understanding birth connectivity associated neurons. While regulators VM DA neurogenesis are known, processes involved in later developmental events, including terminal differentiation axon morphogenesis, less well understood. Recent transcriptional analysis studies developing identified genes...
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...
PURPOSE: To evaluate microscopic behavior and viability of dental pulp stem cells under glucose glutamine deprivation. METHODS: Human tooth tissues were minced in isolated pieces cultured until the desired cellular proliferation for experimental phases. Cells variations both serum presence absence, then those evaluated according to number by MTT assay. The confocal microscopy analyzed cytoskeleton, nucleus, mitochondria integrity. RESULTS: A low concentration favored behavior; culture medium...
The defined self-assembly of peptides (SAPs) into nanostructured bioactive hydrogels has great potential for repairing traumatic brain injuries, as they maintain a stable, homeostatic environment at an injury site, preventing further degeneration. They also present bespoke platform to restore function via the naturalistic presentation therapeutic proteins, such stromal-cell-derived factor 1 (SDF-1), expressed by meningeal cells. A key challenge use SDF protein, however, is its rapid...
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.
Introduction: Tissue Engineering (TE) aims to bio manufacture human tissues, an endeavor that requires a large number of cells, preferably autologous ones. Typically, cell source is unable provide the required amount cells and it necessary such be cultured during prolonged period time. One methodologies used obtain expand in culture explants; however, explants are commonly discarded at moment first passage. Given difficulty obtaining those sources, good alternative would reuse put them back...