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Thread: From laboratory to bedside

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    From laboratory to bedside

    Fiona Wylie, Australian Life Scientist

    15/11/2006 14:56:28

    "It is not that stem cell transplantation doesn't work, it is just that we need more work to figure it out." With this kind of simple optimism, and a little green jasmine tea, Professor Brent Reynolds chatted with Fiona Wylie about life, coincidence and the use of neural stem cells to treat spinal cord injury.

    Brian Reynolds is one of a distinguished list of speakers making up a two-part session, "In the search for a cure for spinal cord injury - from laboratory to bedside", at the Australian Health & Medical Research Congress (AH&MRC) at the Melbourne Convention Centre from November 26 to December 1.

    Reynolds moved from Canada to the Queensland Brain Institute (QBI) at the University of Queensland in 2004. His path to this point has been somewhat unorthodox to say the least, particularly for someone who published a Science paper and devised an important new tool for the entire field during his PhD.

    Immediately after finishing his doctorate in 1994, Reynolds founded a company called NeuroSpheres, based on this new technology.

    "I was the director of research and we worked with large pharma and several biotechnology companies to further develop and protect the technology," Reynolds says. "Today NeuroSphere transplantation technology is licensed to Stem Cell Inc, based in California, who are about to start clinical trials based on technology we developed and patented, which is kind of exciting."

    Impressively, the technology is also the basis of Phase II trials by another company for treating stroke, and at least half a dozen clinical trials starting in 2007-2008.

    The unorthodox route to the QBI began in 1997, when Reynolds opted out of science to study Chinese medicine. He and his family spent the next few years between Thailand, running a yoga centre, and Salt Spring Island off the west coast of Canada, where Reynolds had a Chinese medicine clinic.

    The lure back to science came in 2002 when an old university friend in Vancouver, who was head of business development with a company called StemCell Technologies, contacted him because the company wanted to get into the neural stem cell field.


    Since his arrival in the Sunshine State, Reynolds and his team at the QBI have been developing methodology (soon to be patented) to identify and expand distinct cell populations within a heterogeneous milieu of neural stem cells in culture to benefit transplantation therapies, in particular spinal cord injury.


    "All you are going to need is one tumour in one patient, and it will kill the whole field," he says. "That is what happened in the late '90s with gene therapy."


    As mentioned, Reynolds actually developed the neurosphere assay (NSA), which is now widely used to isolate, propagate and enumerate stem cells derived from the CNS. It is now recognised, however, that not all the neurospheres in a culture are derived from stem cells as first thought. About 90 per cent come from progenitor cells, so the numbers of stem cells represented by the NSA are largely indeterminate. Reynolds is also developing assays to address this problem.


    The second major problem with growing neural stem cells as neurospheres is that only about 10 per cent of the cells turn into neurons. When the cells are given growth factors in culture to drive proliferation, it seems to push them predominantly down the astrocyte lineage (approximately 90 per cent).


    Reynolds' team has come up with a new assay, called the neuroblast assay, which increases the number of neurons that are produced from neurospheres. These are then sorted to give a purity of about 90% neurons. The successful implementation of this technology also depends on being able to identify distinct population of cells within the heterogeneous population of stem and progenitor cells.


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