Isolating Human oligodendrocyte precursor cells

Associate Professor Tailoi Chan-Ling

The University of Sydney

| A cure via repair and regeneration | Neurobiology | Incubator | 2008 | Investigator Led Research |
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Summary

Transplants of healthy cells to replace those damaged during MS could curb if not eliminate disability in people with MS.

Associate Professor Tailoi Chan-Ling and her colleagues are using markers on the surface of early oligodendrocyte cells to pick these from a mixture of neural stem cells. Associate Professor Chan-Ling reports, “My team has being successfully growing human neural stem cell clusters called ‘neurospheres’ in our laboratory for over three years”.

The direct cause of MS remains unknown. What is seen as MS progresses is an attack on oligodendrocytes impairing their ability to replenish the outer covering of myelin around neurons. The result is cumulative disability. A tissue transplant would replace damaged oligodendrocytes with healthy new cells.

Associate Professor Chan-Ling is using advanced technology, called “florescent-activated cell sorting” or FACS, to select early oligodendrocyte cells from neurosphere mixtures to be grown in the lab.

“Our next step will be to transplant human neural stem cells and early oligodendrocyte cells into mouse models of MS to determine the conditions that maximise

The next stage involves actually transplanting these cultivated early oligodendrocyte cells into mice with MS. If transplants can improve the clinical disability in mice with MS, it could open the door to new therapies for the treatment of MS.

Project Outcomes

Dr Tailoi Chan-Ling’s main aim is to isolate human oligodendrocyte precursor cells (OPCs) from human neural stem (NS). Because OPCs only develop into oligodendrocytes - the cells damaged in MS, Dr Chan-Ling’s will generate these cells to understand the cell biology and future use in transplantation studies to replace damaged tissue.

NS cells are able to generate all neural tissue types – this is a great advantage but also a double edged sword. While NS cells can be expanded to large numbers, the ability to control the types of cells that they generate has been elusive. Dr Chan-Ling’s studies will allow the generation of significant numbers of human derived OPCs, thus facilitating our understanding of how these cells function and how best to apply these in the treatment of MS.

The ‘neurosphere assay’ is a means of expanding NS cells into large numbers.  Our previous research has shown that we can generate floating aggregates that contain human OPCs. However, these conditions are not permissive to OPC development in significant numbers.

When grown as neurospheres, NS cells slowly lose the ability to generate OPCs. By determining the effect of various factors, we are now able to increase the proportion of OPCs generated by the neural stem cells. Dr Chan-ling has found that it is crucial to block the bone morphogenic protein (BMP) 4 signalling cascade in order to have successful development of OPCs from human NS cells. To do this Dr Chan-Ling used the small molecule antagonist ‘noggin’.

Dr Chan-Ling was the first to show that noggin significantly increases the number of OPCs derived from human NS cells, thus making possible for the first time a source of human foetal derived oligodendrocytic precursor cells for future application in demyelinating conditions including MS.

Publications

  • Chan-Ling T, Baxter L, Weible II MW, Chu Y and Hughes S, “In vivo characterization of astrocyte precursor cells (APCs) and astrocytes in developing rat retinae; differentiation, proliferation and apoptosis”. (2009) 57 Glia 39-53. Impact Factor: 5.380)(Plus Cover Photo) (e-publication at: www.ncbi.nlm.nih.gov/pubmed/18661555)
  • Weible MW II, Bexkens M and Chan-Ling T, “Effects of noggin on oligodendrocytic lineage elaboration in human fetal spinal cord derived neural precursor cells” In preparation.
  • Weible MW II and Chan-Ling T, “Isolation of Human BMPRII+ Neuronal-Restricted Precursor Cells from Spinal Cord Derived Neural Embryoid Bodies” J. Neurosci. In Preparation.

Updated: 03 January, 2008

Investigator

Grant Awarded

  • Incubator Grant

Total Funding

  • $15,000

Duration

  • 1 year

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Isolating Human oligodendrocyte precursor cells