[Truncated abstract] Olfactory ensheathing glia (OEG) have been demonstrated to improve functional and anatomical outcomes after injury to the nervous system and are currently being trialled clinically. This thesis presents the investigation of two important issues in OEG biology. The first study (Chapter 2) investigates effects of different members of the neuregulin (NRG) family of molecules on the proliferation of OEG, as a means of quickly obtaining large numbers of cells for clinical or experimental use. We report that NRG-1β, but not NRG- 2α or NRG-3, has a significant proliferative effect. Furthermore, we report for the first time that use of different mitogens (forskolin and pituitary extract) commonly used to expand these cells in vitro, can have a significant effect on the responsiveness of OEG to added NRG in subsequent mitogenic assays. OEG grown initially with forskolin and pituitary extract exhibited increased basal proliferation rates in comparison to OEG originally expanded without these factors, and this increased rate of proliferation was sustained for at least 6 days following their withdrawal from the culture medium. We also report for the first time the expression pattern of ErbB2, ErbB3 and ErbB4 receptors on p75-selected OEG, and investigate their contribution to the NRG mitogenic effect by the use of inhibitory ErbB antibodies. Our second study (Chapter 3) seeks to clarify the role of OEG in promoting myelination of central nervous system neurons. In this study we have investigated the myelinating ability of OEG derived from embryonic (EEG), postnatal (PEG) and adult tissue (AEG) both in vitro and in vivo. OEG selected by p75-immunopanning were co-cultured with dissociated cultures of TrkA-dependant embryonic dorsal root ganglion (DRG) neurons. EEG, but not AEG or PEG, successfully myelinated DRG neurons in the presence of serum and/or ascorbate. AEG also failed to myelinate GDNF-dependant embryonic DRG cultures, and growth factor-independent adult DRG cultures. Transplantation of OEG into lysolecithin demyelinated spinal cord demonstrated distinct ultrastructural differences between transplants of OEG derived from animals of different ages. Furthermore, we demonstrate that clearance of degraded myelin from the lesion site appears to be more effective when animals are transplanted with EEG rather than AEG or Schwann cell preparations. These results suggest that myelinating potential of OEG in vitro and behaviour of these cells following transplantation in vivo are developmentally regulated.
| Identifer | oai:union.ndltd.org:ADTP/221209 |
| Date | January 2006 |
| Creators | De Mello, Thalles R. B. |
| Publisher | University of Western Australia. School of Anatomy and Human Biology, University of Western Australia. School of Animal Biology |
| Source Sets | Australiasian Digital Theses Program |
| Language | English |
| Detected Language | English |
| Rights | Copyright Thalles R. B. De Mello, http://www.itpo.uwa.edu.au/UWA-Computer-And-Software-Use-Regulations.html |
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