Griffith University Research Project:
Manipulating the selective activation of olfactory ensheathing cells for the repair of injured spinal cord.
PCSRF Funding - Completed (project has now been incorporated into the Spinal Injury Project)
In 2015 PCSRF funded this exciting project at the Griffith Institute for Drug Discovery (GRIDD), Griffith University under the supervision of project leader Associate Professor James St John.
A recent international trial has shown that olfactory glia can restore some function in paralysed humans. These specialised cells found in the nose, have great potential for repairing the spinal cord. Exciting results from the trial have shown that there is now a real chance of developing a therapy for humans. To make the therapy more effective it now needs to be improved.
The team have discovered that the natural product curcumin can potently stimulate the activity of the olfactory glia. The team now need to further test this natural product to improve the olfactory glia transplant therapy.
The aim of the project is to enhance the activity of the olfactory glia to improve their therapeutic use for the treatment of the injured spinal cord. The project will:
- determine how the natural products enhance the activity of the olfactory glia
- identify alternative natural products that further improve the activity of the cells
- test the natural products with transplanted olfactory glia in spinal cord injury models
Results so far have found that curcumin’s activity is specific to olfactory glia. A similar type of glia, called Schwann cells, which are found in peripheral nerves are not stimulated in the same way as olfactory glia. This means that olfactory glia have properties that are unique and not shared by other glia which reinforces the reason for using olfactory glia for spinal cord repair.
The project has also discovered that the natural products, linckosides, can stimulate olfactory glia to produce more cell connections which would be useful for making new connections within the injury site. Thus it is clear that natural products can stimulate olfactory glia.
The project is now moving into the phase of large scale screening of natural products. The use of robotics and automated analysis means that the team can now screen hundreds of natural compounds each day. The Eskitis Institute holds several hundred thousand natural compounds within the facility Compounds Australia and so it is expected than many more natural compounds that can positively promote neural regeneration will be discovered during this project.
The project has also developed new methods to grow cells in three-dimensions. By growing cells in 3D, the cells make stable connections which means they will survive transplantation better and therefore be able to be more effective in repairing the injury site. It also enables the research team to perform their laboratory experiments on the cells which are more like their natural 3D interactions in the body.
Publications from this project supported by the PCSRF funding:
Tello Velasquez J, Nazareth L, Quinn RJ, Ekberg J, St John JA. 2016. Stimulating the proliferation, migration and lamellipodia of Schwann cells using low-dose curcumin. Neuroscience, 324, 140-50.
Tello Velasquez J, Watts ME, Todorovic M, Nazareth L, Pastrana E, Diaz-Nido J, Lim F, Ekberg JA, Quinn RJ, St John JA. 2014. Low-dose curcumin stimulates proliferation, migration and phagocytic activity of olfactory ensheathing cells. PLoS One, 9, e111787.
Tello VelasquezJ, Yao RQ,Lim F, Han C, Ojika M, Ekberg JAK, QuinnRJ, St JohnJA. Linckosides enhance proliferation and induce morphological changes in human olfactory ensheathing cells. Mol Cell Neurosci 75: 1-13.
Vadivelu RK, Ooi CH, Yao RQ, Tello Velasquez J, Pastrana E, Diaz-Nido J, Lim F, Ekberg JA, Nguyen NT, St John JA. 2015. Generation of three-dimensional multiple spheroid model of olfactory ensheathing cells using floating liquid marbles. Sci Rep. 5:15083.
Harshad K, Jun M, Park S, Barton MJ, Vadivelu RK, St John J, Nguyen NT. 2016. An electromagnetic cell-stretching device for mechanotransduction studies of olfactory ensheathing cells. Biomed Microdevices. 18:45.