MiRNA influences in mesenchymal stem cell commitment to neuroblast lineage development
AbstractMesenchymal Stem Cells (MSCs) are multipotent stromal cells that can self-renew and differentiate into cells from the mesodermal cell lineage. Under specific conditions, MSCs are known to transdifferentiate into the neuronal cell lineage. The aim of this study was to investigate if specific microRNAs (miRNAs) are responsible for neural induction, differentiation and fate specification and if they can induce MSCs to commit to a neuroblast and/or mature neuron cell lineage. The selected miRNAs were miR-107, miR-124 and miR-381, which respectively are known to promote neurogenesis, neural differentiation and neural proliferation. Targeting protein expression by transiently destroying the messenger RNA using miRNAs is an alternative to destroying the gene permanently and, being a transient process, the cells being differentiated should not retain any permanent evidence of this process. The objectives of this study were to culture MSCs from the Wharton’s Jelly, transform these MSCs into neural-like cells using the spent medium from the neuroblastoma cell line SH-SY5Y, and further treat these conditioned cells with retinoic acid to induce further maturation. MSCs were characterised by trilineage differentiation and all three cell types were tested for a series of CD and neural markers. Once characterised, the three cell types were transfected with one of the three selected miRNAs and a target gene for each miRNA was analysed but results were sub-optimal. The MSCs and neural-like derivatives were then tested for a selection of neural markers. Once again results provided limited information, however it was observed that miR-107 and miR-124 have the potential to induce MSCs to differentiate into neural-like cells and that these miRNAs may also induce intermediate neural progenitors and immature neuron cell types to differentiate further.
PublisherUniversity of Wolverhampton
TypeThesis or dissertation
DescriptionA thesis submitted in partial fulfilment of the requirements of the University of Wolverhampton for the degree of Professional Doctorate in Biomedical Science.
SponsorsMalta Government Scholarship Scheme.
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