UWA Associate Professor Stuart Hodgetts and PhD student Sarah Lovett are using human bone marrow stem cells (BMSCs) to promote an endogenous host response after spinal cord injury (SCI), by isolating stromal cells found in a patient’s own bone marrow and transplanting them back into the injury site in animal models.
A/Prof Hodgetts says the objective is to transplant these multipotent stromal stem cells into the spinal cord to promote the survival of existing neurons and improve repair at the injury site.
“We believe the donor BMSCs are responsible for producing an endogenous repair mechanism, essentially providing factors to help the host system repair itself. Our animal models have shown BMSCs promote good functional improvement beyond many other cell types used over the last 5–10 years,” he says.
Ms Lovett says the research does not specifically aim to differentiate BMSCs into neurons or supportive glial cells, but instead reduce the amount of secondary damage that occurs after the initial injury.
“We found BMSCs reduce inflammation in the injury site as well as reduce secondary damage. Also, while extracting cells from bone marrow might be regarded as an invasive procedure, it’s actually quite routine,” she says.
“If you can take bone marrow from an injured patient, after about 3 weeks’ culture you would have enough cells to transplant back into that person.”
Ms Lovett uses a contusion model in rats that best replicates the most common SCI in humans.
“The animals show good functional recovery if BMSCs are transplanted into the cord a week after injury. However, BMSCs are soon destroyed by the animal’s immune response against them,” she says.
Prof Hodgetts says part of the research is to modulate the immune response by inhibiting “TNF-alpha” molecules and “natural killer”, immune cells that may target the transplanted cells.
“Interestingly, within that window of four weeks, BMSCs are able to induce a response that markedly improves the locomotory ability of these animals.”
“If we can improve BMSC survival, we may be able to get them to further improve functional recovery for longer,” he says.
Prof Hodgetts’ Fellowship and this SCI research project is funded by the Neurotrauma Research Program of Western Australia.
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