Development of unrestricted somatic stem cells from human umbilical cord blood into the neuronal phenotype in vitro.

Human umbilical cord blood stem cells are increasingly considered in cell-based therapeutic strategies for regeneration of different tissues. One subpopulation, unrestricted somatic stem cells (USSC), are a form of pluripotent, neonatal, non-hematopoietic stem cells which have the potential to differentiate into the neural lineage. However, the molecular and functional characterization of the neural phenotype and evaluation of the degree of maturity of the resulting cells are still lacking. In this study we examined the neuronal differentiation and maturation of USSC induced by XXL-medium, a defined composition of growth and differentiation factors. Specially, we investigated the expression of different neuronal markers and their enrichment in USSC cultures during XXL-medium incubation. Further, differentiation into the dopaminergic phenotype was examined. In addition, the induction of Nurr1, a factor regulating dopaminergic neurogenesis, and an enrichment of USSC expressing tyrosine hydroxylase, the key enzyme of dopaminergic neurons, could be demonstrated. Functional differentiation of USSC was confirmed by patch-clamp recordings that revealed functional voltage-gated sodium-channels in laminin pre-differentiated USSC. Additionally, high performance liquid chromatography was performed showing synthesis and release of the neurotransmitter dopamine by USSC-derived cells, thus correlating well with the detection of dopaminergic markers, transcripts and proteins. In conclusion this study provides novel insight into the potential of unrestricted somatic stem cells from human umbilical cord blood to acquire a neuronal phenotype and function. [ABSTRACT FROM AUTHOR]