The transplantation and differentiation of glial-biased
stem-like cells from peripheral nerves.
Doctoral thesis, UCL (University College London).
The generation of Schwann cells is preceded by the generation of the Schwann cell precursor (SCP), a cell type that differs in a number of ways from migrating crest cells and Schwann cells. SCPs can be considered as glial-biased stem-like cells and I report that they have favourable properties as myelin repair cells. In particular, they are able to migrate through normal central nervous system tissue to reach demyelinated lesions, unlike Schwann cells, while at the lesion site they differentiate to generate peripheral type myelin. Although this finding was promising, in order for SCPs to be suitable for transplantation paradigms in a clinical setting, I wanted to assess whether they could be administered intravenously and were able to cross the blood-brain barrier to reach demyelinated lesions. Even though I found that SCPs express α4 integrin, an important molecule for the passage of cells through the blood-brain barrier, they did not cross the blood-brain barrier. However, the expression of α4 integrin in SCPs revealed, in a different set of experiments, that this integrin can be used as a novel marker for SCPs. In order to further understand why SCPs gave rise to Schwann-like cells in the central nervous system, experiments were designed to investigate the mechanisms that control the maturation of SCPs, and in particular the role of neuregulin I, an essential survival factor for SCPs that has also been suggested to promote their maturation to Schwann cells. By infecting SCPs with an anti-apoptotic gene to ensure their survival, I showed that, even in simple chemically defined culture medium, SCPs matured to Schwann cells in vitro. This suggests that neuregulin I signalling is not required for the maturation of SCPs to Schwann cells
|Title:||The transplantation and differentiation of glial-biased stem-like cells from peripheral nerves|
|Additional information:||Authorisation for digitisation not received|
|UCL classification:||UCL > School of Life and Medical Sciences > Faculty of Life Sciences > Biosciences (Division of) > Cell and Developmental Biology|
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