Repairing The Injured Spinal Cord: Potential For Human Olfactory Ensheathing Cells
Funder
National Health and Medical Research Council
Funding Amount
$255,990.00
Summary
Spinal cord injury is a major cause of morbidity, particularly among young people involved in road accidents and sports injuries. Finding ways to treat paraplegia is a major goal of neuroscience research. Recently, there has been considerable interest in a special cell found in the olfactory system, the ensheathing cell, which has been found to support regeneration in the spinal cord. Our laboratory has shown that injection of these ensheathing cells into the completely cut spinal cord of adult ....Spinal cord injury is a major cause of morbidity, particularly among young people involved in road accidents and sports injuries. Finding ways to treat paraplegia is a major goal of neuroscience research. Recently, there has been considerable interest in a special cell found in the olfactory system, the ensheathing cell, which has been found to support regeneration in the spinal cord. Our laboratory has shown that injection of these ensheathing cells into the completely cut spinal cord of adult rats can lead to limited functional recovery of hindlimb movement. We used peripheral ensheathing cells because, in humans, such cells can be obtained relatively easily and they reduce problems of tissue rejection. We found that peripheral cells are as effective as previous reports using central ensheathing cells. Our overall aim now is to advance towards the use of olfactory cells in human spinal cord injury, by trialing 3 procedures of clinical relevance: a) to test whether human olfactory cells can also support functional recovery in rats. Human cells can be obtained from the nose by a simple biopsy procedure. If they able to support regeneration, this will open the way for their use in autografts in human paraplegia. b) to delay the time when the olfactory cells are applied to the injured cord. At present, neurosurgeons are not be willing to treat the cord immediately after the injury, because of the risk of causing further damage. This trial is designed to test whether delayed treatment is still effective. c) to test the effectiveness of the cells after bruising, rather than cutting, the cord. Bruising is a more common type of injury in people, hence it is necessary to know how these cells respond to this type of damage. These procedures have been chosen to move our basic research closer to clinical application. Although treatment in humans is still a long way off, these basic studies are essential if conditions like paraplegia are eventually to become treatable.Read moreRead less
Cellular And Molecular Mechanisms Of Neuronal Repair By Olfactory Ensheathing Cells
Funder
National Health and Medical Research Council
Funding Amount
$218,250.00
Summary
Traumatic injury to the human brain and spinal cord often results in permanent disability. A major reason is that nerve fibres which act as cables connecting different parts of the nervous system are injured and fail to regrow. Failure of adequate repair is due to the fact that the central nervous system is a hostile environment, lacking in growth promoting stimuli and instead possessing growth inhibitory properties. One of the experimental methods used to alter this environment is the transplan ....Traumatic injury to the human brain and spinal cord often results in permanent disability. A major reason is that nerve fibres which act as cables connecting different parts of the nervous system are injured and fail to regrow. Failure of adequate repair is due to the fact that the central nervous system is a hostile environment, lacking in growth promoting stimuli and instead possessing growth inhibitory properties. One of the experimental methods used to alter this environment is the transplantation of olfactory ensheathing cells into the injury site. Ensheathing cells normally support the nerve fibres involved in the sense of smell. Tissue culture studies show that these cells produce on their surface specific types of molecules as well as soluble growth factors that could interact with nerve fibres to promote growth. Although experiments in which ensheathing cells have been injected into rat spinal cords, have resulted in varying degrees of recovery, the question of how they are able to do this remains unknown. The study proposed here will use tissue culture and in vivo models to investigate how ensheathing cells interact with their surrounding cells. In particular we will examine how soluble factors and direct membrane contact contribute to the regeneration of nerve fibres. We will also examine the effects that ensheathing cells have on non-neuronal cells such as astrocytes and oligodendrocytes and vice-versa. A significant outcome of this project is new insight into the complex cellular interaction that occurs to bring about repair in the central nervous system. The findings will pave the way for the future development of olfactory ensheathing cells as an effective therapeutic agent of nerve repair. This could also include genetic manipulation of ensheathing cells such that their properties are optimised specifically to promote regrowth of nerve fibres.Read moreRead less
Cell Type Specification In Developing CNS: Functional Analysis Of Sox14
Funder
National Health and Medical Research Council
Funding Amount
$468,055.00
Summary
The central nervous system (CNS) is the most complex organ in the body. The vast majority of nerve cells in the CNS are classified as 'interneurons'. These cells relay sensory information and motor commands within the CNS. Abnormal functioning of interneurons is likely to be the underlying cause of some, if not many, human nervous system diseases. However, very little is known of the precise anatomy and function of interneurons, which genes control their development, and how these functions are ....The central nervous system (CNS) is the most complex organ in the body. The vast majority of nerve cells in the CNS are classified as 'interneurons'. These cells relay sensory information and motor commands within the CNS. Abnormal functioning of interneurons is likely to be the underlying cause of some, if not many, human nervous system diseases. However, very little is known of the precise anatomy and function of interneurons, which genes control their development, and how these functions are maintained in the adult. This has been largely due to a lack of efficient and reliable methods to identify and study interneurons. We have previously discovered that a gene termed Sox14 is active in distinct interneuron groups in the embryonic brain and spinal cord. Sox14 is a member of the Sox gene family, many of which act as genetic switches to control cell and tissue development. We found that Sox14 has been extremely well conserved throughout evolution and is active in similar interneuron groups in a number of animal species. These studies led us to hypothesise that Sox14 controls a critical molecular step in the generation of certain interneurons that may be involved in reflexes, locomotion or motor coordination. In this project, we will investigate both the role of Sox14 in interneuron development and the functions of interneurons in which this gene is active. We will do so by combining modern molecular and genetic techniques with physiological approaches. This project will reveal critical molecular steps in CNS development and determine the functions of a specific group of interneurons. To this end, we will generate mouse strains in which a specific group of interneurons are genetically marked and can be manipulated during development. We envisage that these mice with 'modified brain circuits' will become unique resources for future investigations of selected interneuron types and their functions.Read moreRead less
Translation Of Effective Interventions In Injury Prevention And Trauma Care To A Chinese Setting
Funder
National Health and Medical Research Council
Funding Amount
$349,407.00
Summary
Evidence informed injury policy is not currently well developed in China. This research project will provide measures of the effectiveness of both a trauma care protocol in a hospital setting, and an intervention program for novice driver education-training in China, and will therefore contribute to the building of an evidence based injury prevention capacity in China.