Somatic stem cells: properties and potential for regenerative medicine

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

Amniotic fluid stem cells increase embryo survival following injury.

Although amniotic fluid cells can differentiate into several mesenchymal lineages and have been proposed as a valuable therapeutic cell source, their ability to undergo terminal neuronal differentiation remains a cause of controversy. The aim of this study was to investigate the neuronal differentiation ability of the c-Kit-positive population from GFP-transgenic rat amniotic fluid, amniotic fluid stem (AFS) cells, and to assess how they affected injury response in avian embryos. AFS cells were found to express several neural stem/progenitor cell markers. However, no overt neuronal differentiation was apparent after either treatment with small molecules known to stimulate neuronal differentiation, attempts to differentiate AFS cell-derived embryoid body-like structures, or grafting AFS cells into environments known to support neuronal differentiation (organotypic rat hippocampal cultures, embryonic chick nervous system). Nonetheless, AFS cells significantly reduced hemorrhage and increased survival when grafted at the site of an extensive thoracic crush injury in E2.5 chick embryos. Increased embryo survival was induced neither by desmopressin treatment, which also reduced hemorrhage, nor by grafting other mesenchymal or neural cells, indicating a specific effect of AFS cells. This was found to be mediated by soluble factors in a transwell coculture model. Altogether, this study shows that AFS cells reduce tissue damage and increase survival in injured embryos, providing a potentially valuable tool as therapeutic agents for tissue repair, particularly prenatal/perinatal repair of defects diagnosed during gestation, but this effect is mediated via paracrine mechanisms rather than the ability of AFS cells to fully differentiate into neuronal cells