Transplanted CNS stem cells form functional synapses in vivo.
An understanding of developmental mechanisms and new cell therapies can be achieved by transplantation into the nervous system. Multipotential stem cells have been isolated from the foetal and adult central nervous system (CNS). Immortalized and primary precursor cells integrate into the developing brain generating both neurons and glia as defined by immunological and morphological criteria. Here we show for the first time that in vitro-expanded CNS precursors, upon transplantation into the brains of rats, form electrically active and functionally connected neurons. These neurons exhibit spontaneous and evoked postsynaptic events and respond to focal glutamate application. Donor cells were grafted into the foetal hippocampus, and the amplitude and frequency of spontaneous synaptic events were monitored in the grafted cells in area CA1 for the first month of postnatal life. The formation of synapses onto grafted neurons indicates that grafted CNS stem cells can be used to study synaptic development in vivo and has important implications for clinical cell replacement therapies.
Auerbach
J M
JM
Laboratory of Molecular Biology, National Institute of Neurological Disorders and Stroke, NIH, 36 Convent Drive,Bldg 36 Room 5A29 MSC 4157, Betheda, MD 20892-4157, USA.
Eiden
M V
MV
McKay
R D
RD
D000818:Animals; D016380:Brain Tissue Transplantation / Q000502:physiology*; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology* / Q000196:embryology; D019706:Excitatory Postsynaptic Potentials; D016332:Fetal Tissue Transplantation / Q000502:physiology*; D017930:Genes, Reporter; D049452:Green Fluorescent Proteins; D066298:In Vitro Techniques; D008164:Luminescent Proteins / Q000032:analysis / Q000235:genetics; D008564:Membrane Potentials; D009474:Neurons / Q000502:physiology* / Q000637:transplantation*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012190:Retroviridae; D013234:Stem Cells; D013569:Synapses / Q000502:physiology*; D014162:Transfection
D008164:Luminescent Proteins; D049452:Green Fluorescent Proteins