Developing an olfactory cell therapy for spinal cord injury

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a) Issues with spinal cord repair and regeneration

b) How does our therapy work?

c) What happens after?

a) Issues with spinal cord repair and regeneration

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•The site of injury after the trauma is like a wreckage from a road accident.


•The debris from a crash has to be cleared up before the roads can open up again and the traffic can resume.


•The body can clear debris at the spinal cord injury site, but not very effectively. It takes a long time and initiates the glial scarring that can hinder any repairs.


•Glial scars aren't like the scars we get on our skin, but are the same idea - to protect the body and initiate the healing process in the central nervous system.


•Our therapy utilises the natural functions of olfactory ensheathing cells (supporting glial cells from the olfactory (sense of smell) system, to clean up debris in the injured spinal cord and to interact with the cells of the glial scar (astrocytes). Something that other cells cannot do.

B) How does our therapy work

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The core approach to our spinal cord injury therapy is to transplant cells known as olfactory ensheathing cells (OECs) taken from the nose and put into the injured spinal cord. In order to successfully achieve this, we have taken a multi-step approach to the problem.

Purification

•The normal roles of OECs are to aid in the growth, guidance and regeneration of the neurons in the olfactory nerve. The neurons of the olfactory nerve are, so far, the only neurons in the body that are known to regenerate and they do this on a daily basis. 


•The olfactory system is the system we use to smell with.


•OECs are found in two places in the olfactory system - closer to the outside of the nose in what is known as the 'lamina propria', or further up towards the brain in what is known as the 'olfactory bulb'. Studies around the world that have used OECs for regeneration therapies have used cells from both places, however the OECs from the 'lamina propria' are more easily accessible by surgeons for biopsies, and create fewer complications than taking cells from the olfactory bulb. This is why we are using cells from the 'lamina propria'.  


•After biopsy, a purification process needs to take place to sort out the OECs from the numerous other cells that are found in the lamina propria of the nose. These other cells are not useful for the regeneration of the injured spinal cord and mixed cell transplants could lead to variable outcomes for patients.

Cleaning up the Injury Site

•One of the recently discovered cellular functions of OECs are their ability to phagocytose (eat up cell debris and bacteria).


•Neurons in the olfactory system die off all the time, due to being exposed to the atmosphere, and noxious chemicals, bacteria and viruses that we breath in. These dead neurons need to be cleaned up in order to allow new neuron growth. OECs can clean up the remaining dead cell debris. 


•This extremely useful function can also be applied to the injured spinal cord, where transplanted OECs can be stimulated to clean up the dead neurons or even bacteria that have entered the injury site, making a more favourable environment for new neuron growth.

Drug Discovery

 • Our group has demonstrated that OEC migration, and the extension of a part of a neuron called an axon can be stimulated by proteins naturally found in the body called growth factors. 


 • We have also shown that we can utilise naturally occurring chemical compounds (from plants and marine invertebrates) to enhance the repair properties of OECs. 


 • We are therefore screening thousands of compounds (in association with Griffith University's Compounds Australia and NatureBank) in an effort to find more chemicals that can be applied to OECs in the dish, and before transplantation to enhance their number, health and repair abilities. 

Growing cells in 3 Dimensions

•Most of the experiments and trials done around the world with OECs or other types of cells for neural repair have injected their cells of interest (into the injury site or into tissue surrounding the injury site) in the form of a solution of cells.


•Our group is taking a different approach, by transplanting the OECs in a 3-dimensional (3D) structure.


•3D structures both protect the transplanted cells from the harsh environment of the injury site, and potentially create a safe environment for the growth of more cells.


•Our lab has created a world-first technology to create so-called "Naked Liquid Marbles". These marbles allow small 'spheroids' of cells to develop inside a droplet of liquid on a superhydrophobic surface. For more information see here.


Transplantation

•Once the cells have been purified, enhanced with compounds, grown and put into a 3D structure, they are ready for transplantation. 


•At Griffith University we have medical doctors, veterinarians and scientists working together to develop the best technique to get the cells into the right place in the spinal cord injury site, at the right time. 


•These researchers then analyse the recovery and function of the animals in a series of non-invasive observational tests.

C) What Happens After?

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Sustained Functional Therapy/Rehabilitation

 •OEC transplantation trials have been taking place around the world for the past 20 years with some amazing successes. What has been realised is that for any cell transplantation therapy that occurs, rehabilitation, or as we call it "Sustained Functional Therapy" (SFT) also needs to take place. Those trials that did not employ SFT did usually not see improvement in their patients. 


•SFT (rehabilitation) takes the form of assisted exercises or activity based therapy that moves the entire body. This can take place in different forms such as Locomotor training; Load bearing; Functional Electrical Stimulation therapy; Resistance training and Aerobic fitness. 


•Sustained functional therapy involves neuroplasticity and retrains and enhances the existing neural circuits in the brain and spinal cord and strengthens the newly created connections in an injury site that has been transplanted with an OEC construct.


•For our animal studies, we use non-invasive tests such as 'open field test', 'ladder rung tests', and DigiGait™ analysis and mouse wheels. For humans, we are working with industry partners such as Making Strides, and The Next Step to help patients undergo SFT/rehabilitation.