Somatic stem cells: properties and potential for regenerative medicine.
Doctoral thesis, UCL (University College London).
Stem cells play fundamental roles in embryonic development, tissue homeostasis and have great potential in regenerative medicine. The main aims of this study were: i) to elucidate the properties and neural differentiation potential of somatic stem cells from different sources focusing on the analysis of stem cells with low immunogenicity and/or suitable for autologous cell therapy, amniotic fluid (AFSC) and adipose tissue-derived stem cells (ADSC), respectively; ii) to investigate a putative neural stem/progenitor cell niche in the choroid plexus (CP), organ that plays crucial roles in cerebrospinal fluid secretion and brain homeostasis. Unlike previously suggested, I found that AFSCs do not harbour significant neurogenic potential, as assessed by treatment with neurogenic small molecules, transplantation onto hippocampal organotypic cultures and within the chick nervous system. However, in a severe embryonic injury model grafted AFSCs reduced haemorrhage and significantly increased embryo survival via paracrine mechanisms. I then established and characterized ADSCs cultures derived from the fat of paediatric patients. They expressed markers of embryonic stem cells, mesenchymal and neural tissues, and displayed significant plasticity, as indicated by their ability to differentiate both into bone and cartilage upon appropriate stimulation, to home into the chick nervous system, and to be relatively rapidly reprogrammed to “induced pluripotent stem cells”. Altogether, though ADSCs seem more plastic than AFSCs, both provide valuable tools for developing novel therapeutic approaches and analyzing cell phenotype modulation. Finally, I showed the presence of neural precursors, neuroblasts and neuron-like cells within the CP in different species by analysis of neural markers and BrdU incorporation in vivo and in organotypic cultures, and demonstrated innervation of the CP at early developmental stages. Altogether these findings suggest the existence of a neural regulatory network within the CP that may play a crucial role in modulating its function in the developing and post-natal brain.
|Title:||Somatic stem cells: properties and potential for regenerative medicine|
|UCL classification:||UCL > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Child Health|
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