Blastula-Stage Stem Cells Can Differentiate into Dopaminergic and Serotonergic Neurons after Transplantation

Embryonic stem cells develop into functional dopaminergic neurons after transplantation in a Parkinson rat model

“…We have shown previously that mouse ES cells transplanted to normal mice or 6-hydroxydopamine (OHDA)-lesioned rats can differentiate spontaneously into tyrosine hydroxylase (TH)-positive and serotonin (5HT)-positive neurons. This differentiation is likely not caused by a specific inductive signal from the host brain, because similar neuronal differentiation occurs after placement in the kidney capsule (11). In our previous study (11), grafts frequently showed heterogeneous morphology and often became very large, disrupting the cytoarchitecture at the implantation site, which prevented the possibility for functional integration.…”

“…This differentiation is likely not caused by a specific inductive signal from the host brain, because similar neuronal differentiation occurs after placement in the kidney capsule (11). In our previous study (11), grafts frequently showed heterogeneous morphology and often became very large, disrupting the cytoarchitecture at the implantation site, which prevented the possibility for functional integration. Because neurons develop from ES cells even when implanted outside the central nervous system (11) and ectoderm develops into neural tissue when cellto-cell communication is disrupted by dissociation of the cells (12)(13)(14), we hypothesized that dilution of ES cells into single-cell suspensions of low ES cell concentrations would result in neuronal development.…”

“…In our previous study (11), grafts frequently showed heterogeneous morphology and often became very large, disrupting the cytoarchitecture at the implantation site, which prevented the possibility for functional integration. Because neurons develop from ES cells even when implanted outside the central nervous system (11) and ectoderm develops into neural tissue when cellto-cell communication is disrupted by dissociation of the cells (12)(13)(14), we hypothesized that dilution of ES cells into single-cell suspensions of low ES cell concentrations would result in neuronal development. A low cell concentration decreases ES cell-to-cell contact and increases the influence from the adult host striatum, which in contrast to adult neurogenic regions may restrict cell migration and proliferation, thus allowing default differentiation (15)(16)(17) into neurons in this paradigm.…”

“…ES cells are self-renewing and multipotent cells derived from the inner cell mass of the preimplantation blastocyst (11). We have shown previously that mouse ES cells transplanted to normal mice or 6-hydroxydopamine (OHDA)-lesioned rats can differentiate spontaneously into tyrosine hydroxylase (TH)-positive and serotonin (5HT)-positive neurons.…”

Embryonic Stem Cells: New Possible Therapy for Degenerative Diseases That Affect Elderly People

“…This allowed the Parkinson symptoms to reverse in 50% of the animals, while only 25% of them developed brain tumors (70,71). If a large number of ES cells are implanted into the brain, they grow into every cell type and form teratomas in all cases, eventually killing their host (72). More recently, Kim et al (73) have characterized the electrophysiological and behavioral properties of highly enriched populations of mouse ES-derived midbrain neural stem cells, able to functionally integrate into host tissue and improve symptoms in a rodent model of PD.…”