Neurogenesis and Stem Cells

GRC Neurogenesis and stem cell group

Brain damage and neurological disorders, caused by injury or disease affect over 1.6 million (12%) Australians, often resulting in numerous associated comorbidities and lifelong disabilities.

The Neurogenesis and Stem Cell group within the GRC uses self-renewing and multipotent human neural stem cells (hNSCs), multipotent mesenchymal stem cells (MSCs) and induced pluripotent stem (iPS) cells as in vitro models to study human neurogenesis and neurological disorders. In order to overcome the challenges associated with the use of stem cells in the repair of neurological disorders and brain damage, our understanding and ability to manipulate the regulatory mechanisms controlling neural cells, lineage-specific differentiation and their function is crucial.

The heparan sulfate (HS) and chondroitin sulfate (CS) proteoglycans (PGs) are widely distributed in the body and the nervous system, primarily in the extracellular matrix. Multiple studies in rodent models have identified a role for these proteins during normal development of the nervous system as well as in the maintenance of stem cell pools in the adult. With PGs widely present in the central nervous system, these important molecules are likely key factors mediating numerous stages of human neural lineage specification. What has yet to be elucidated is how these PGs contribute to the control of neural stem cell (NSC) lineage regulation, proliferation and differentiation in humans.

Neural stem cells (NSCs) are retained in the adult brain in discrete locations where they maintain the ability to self-renew and differentiate into neural cell lineages – neurons, astrocytes and oligodendrocytes. Isolated NSCs can be propagated in vitro in the presence of growth factors as free-floating neurospheres. Neural cell lineages can also be derived from embryonic stem cells (ESCs), and immortalised progenitors which can be expanded as an adherent monolayer circumventing the challenges associated with long-term neurosphere culture.

Multipotent mesenchymal stem cells (MSCs) and induced pluripotent stem (iPS) cells have a large capacity for self-renewal and differentiate into numerous cell types including neural lineages. In addition, these cells can contribute to the localised extracellular matrix and microenvironment to provide structural support to mediate cell-matrix interactions and are excellent models to derive large numbers of progeny as well as to examine lineage fate and the role of the niche in mediating the cell-cell and cell-matrix interactions associated with neurogenesis. Currently these cells are being used as a model within the GRC to examine neural differentiation and the neural niche with the aim of developing localised and targeted brain damage repair strategies.