Our lab investigates neural stem cells. We explore their fundamental biology and their capacity to regenerate injured/diseased tissue. We consider both exogenous cell transplantation paradigms as well as endogenous strategies to activate the resident neural stem and progenitor cells in animal models of injury/disease. In considering the potential success of our neural repair strategies we use cellular, structural and functional outcomes as measures of success. We take an interdisciplinary approach to exploring and enhancing the regenerative potential of the central nervous system.
A) Stem Cell Biology:
In order to harness the potential of neural stem cells for the ultimate goal of regenerative medicine, it is essential to understand the mechanisms that regulate neural stem and progenitor cell behaviour. We have recently found a novel stem cell in the developing nervous system that persists into adulthood along the entire neuraxis, essentially redefining the neural stem cell lineage in the CNS. Both genetic and epigenetic factors have been shown to control cell fate decisions and we using state-of-the-art imaging techniques to examine the behaviour of individual stem cells as they proliferate to form colonies and differentiate into specific neural cell types. We can exquisitely control the microenvironment as well as modify candidate gene expression to determine what factors are important for controlling the fundamental behaviour of neural stem and progenitors cells.
B) Electric Field on Neural Stem Cell Migration:
We have developed a novel technique to enhance neural precursor cell migration both in vitro and in vivo. The application of clinically relevant electric fields promotes the directed and rapid migration of neural precursor cells in the central nervous system. We are collaborating with Dr. Milos Popovic and others to investigate the potential of this novel therapeutic to promote neural repair. Moreover, we are interested in whether the application of electric fields also effects the fundamental biology of neural stem cells and their progeny and are using a variety of methodologies to explore this.
C) Stem Cells to Treat the Injured Nervous System:
The potential for stem cells to treat a variety of currently untreatable human diseases has received worldwide attention. In particular, research in animal models and some early clinical trials have stem cells could potentially be used to treat patients suffering from disorders of the nervous system, such as stroke and spinal cord injury, conditions which are devastating to the patients, their families, and society as a whole. Transplantation studies using neural stem and progenitor populations are one strategy to promote tissue repair and we are actively pursuing these paradigms with novel cell sources combined with bioengineering strategies.
Stroke can happen at any age. While most prominent in the aged population, it can occur perinatally and into adulthood. We are taking two approaches to promote repair of the stroke injured brain. First, the use of factors to activate stem cells that are already resident in the mammalian brain to ask whether this can promote “self-repair” mechanisms. Behavioural assays for sensory-motor function as well as cognition are employed- arguably the most clinically relevant outcome measurements. In adult models of stroke we are transplanting clinically relevant human derived neural precursor cells into the injured brains. We want to know if cell integration into the host tissue is required for functional recovery or whether the transplanted cells mediate their benefit by releasing factors that promote host plasticity. These are fundamental questions that will help to focus future stem cells based therapies to treat stroke.
C-2) Spinal Cord Injury
Spinal cord injury (SCI) is a devastating event with major social and economic implications. We are using a combination of strategies including tissue engineering and endogenous stem cell activation in an attempt to achieve functionally significant repair and regeneration in rodent models of SCI. In collaboration with neurosurgeons and bioengineers we are combining our efforts to replace lost cells; create devices that promote neural stem cell migration and provide an local environment that promotes repair and recovery following neurotrauma.
C-3) Treatment of Brain Injury in Children
Each year over 140,000 children and teenagers suffer a brain injury due to trauma, stroke, cerebral palsy, and brain cancer. Children are often left with permanent physical, psychological, and neurological problems. Currently there are no effective medical therapies to help brain recovery and reduce disability following an acquired brain injury, including brain irradiation. We are interested in applying our stem cell activation strategies, including drugs, exercise and rehabilitation, to encourage brain repair after an injury.