Unrestricted somatic stem cells from human umbilical cord blood can be differentiated into neurons with a dopaminergic phenotype.
Recently, it has been shown that human unrestricted somatic stem cells (USSCs) from umbilical cord blood represent pluripotent, neonatal, nonhematopoietic stem cells with the potential to differentiate into the neural lineage. However, 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 addressed the question of neuronal differentiation and maturation induced by a defined composition of growth and differentiation factors (XXL medium). We demonstrated the expression of different neuronal markers and their enrichment in USSC cultures during XXL medium incubation. Furthermore, we showed enrichment of USSCs expressing tyrosine hydroxylase (TH), an enzyme specific for dopaminergic neurons and other catecholamine-producing neurons, accompanied by induction of Nurr1, a factor regulating dopaminergic neurogenesis. The functionality of USSCs has been analyzed by patch-clamp recordings and high-performance liquid chromatography (HPLC). Voltage-gated sodium-channels could be identified in laminin-predifferentiated USSCs. In addition, HPLC analysis revealed synthesis and release of the neurotransmitter dopamine by USSC-derived cells, thus correlating well with the detection of TH transcripts and protein. 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.
Greschat
Susanne
S
Molecular Neurobiology Laboratory, Heinrich-Heine University, D-40225 Düsseldorf, Germany.
Schira
Jessica
J
Küry
Patrick
P
Rosenbaum
Claudia
C
de Souza Silva
Maria Angelica
MA
Kögler
Gesine
G
Wernet
Peter
P
Müller
Hans Werner
HW
D000818:Animals; D002453:Cell Cycle / Q000187:drug effects; D002454:Cell Differentiation; D002478:Cells, Cultured; D003470:Culture Media / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism*; D005312:Fetal Blood / Q000166:cytology*; D006801:Humans; D009474:Neurons / Q000378:metabolism / Q000502:physiology*; D010641:Phenotype; D051381:Rats; D015222:Sodium Channels / Q000378:metabolism / Q000502:physiology; D013234:Stem Cells / Q000378:metabolism / Q000502:physiology*
D003470:Culture Media; D015222:Sodium Channels; D004298:Dopamine