Neurogenesis and Neural Transplantation

Regenerative therapies for brain repair. Our laboratory is interested in the idea that stem cells can repair the damaged brain. There are two broad strategies we are pursuing. The first is neural transplantation. It is an approach that has had some success clinically for Parkinson’s disease and involves the transplantation of new neurons directly into the patient’s brain in order to functionally compensate for those lost to the disease. We are continuing to explore and optimise this as a therapeutic option not only for Parkinson’s disease but also for other neurological conditions such as stroke and motor neuron disease. The second strategy is based on the idea that the brain retains some capacity for ‘self-repair’ through neurogenesis. Part of our research program seeks to characterise the brain’s own capacity to generate new neurons in response to injury and to manipulate this response in favour of therapeutic outcomes.

Project SupervisorProjects

Lachlan Thompson

lachlant@unimelb.edu.au

Project 1: Parkinson’s disease in a dish.

Supervisors: Dr Lachlan Thompson, Dr Jennifer Hollands.

Pluripotent stem cells can be used to generate a wide variety of neuronal subtypes relevant for repair of the central nervous system. Recently we showed that cortical neurons can be transplanted into the part of the cortex damaged by a focal stroke and have a remarkable capacity to integrate into the existing host circuitry in order to restore motor function. This project will extend on these findings to explore whether we can restore multiple circuits in more severe models of stoke affecting multiple brain region by transplanting multiple neuronal cell types. The project will utilise a number of in vitro and in vivo techniques including: human pluripotent cell culture; immunochemistry; stereotaxic surgery; analysis of animal behaviour; histology and microscopy.

Project 2: Rebuilding the brain after stroke.

Supervisors: Dr Lachlan Thompson, Dr Jennifer Hollands.

Pluripotent stem cells can be used to generate a wide variety of neuronal subtypes relevant for repair of the central nervous system. Recently we showed that cortical neurons can be transplanted into the part of the cortex damaged by a focal stroke and have a remarkable capacity to integrate into the existing host circuitry in order to restore motor function. This project will extend on these findings in order to explore whether we can restore multiple circuits in more severe models of stoke affecting multiple brain region by transplanting multiple neuronal cell types. The project will utilise a number of in vitro and in vivo techniques including: human pluripotent cell culture; immunochemistry; stereotaxic surgery; analysis of animal behaviour; histology and microscopy.

Project 3: Development of Stem Cell based therapies for Motor Neuron Disease.

Supervisors: Dr Lachlan Thompson, Dr Stefano Frausins.

Recent advances in stem cell biology allow for the on-demand generation of spinal motor neurons from human pluripotent stem cells. Our laboratory has been exploring the possibility that these neurons can be implanted directly into the spinal cord in order to functionally compensate for those lost to
the disease process. This project will seek to understand
the capacity for implanted motor neurons to appropriately integrate into host circuitry, including innervation of peripheral targets. We will also explore the concept that the implanted neurons can protect the host neurons from the disease process.