Development of neuronal networks from single stem cells harvested from the adult human brain.
OBJECTIVE
It was long held as an axiom that new neurons are not produced in the adult human brain. More recent studies, however, have identified multipotent cells whose progeny express glial or neuronal markers. This discovery may lead to new therapeutic strategies against central nervous system disorders by transplanting stem cells that have been propagated in vitro. Still, it is not known whether stem cells from the adult human brain retain the potential to mature into neurons that integrate and communicate in a network.


METHODS
We cultured cells from the ventricular wall of the adult human brain as monoclonal neurospheres. After two passages, the neurospheres were dissociated and the cells were allowed to differentiate. After 4 weeks of maturation, the cells were studied by immunocytochemistry, confocal microscopy, and whole-cell patch-clamp.


RESULTS
We show that monoclonal stem cells harvested from the ventricular wall of the adult human brain develop into mature neurons with functional glutamate receptors and glutamatergic nerve terminals. By patching pairs of cells simultaneously, we also present direct evidence for synaptic communication between neurons developed from the same monoclonal cell.


CONCLUSIONS
Neural stem cells harvested from the adult human brain retain the potential to mature into fully differentiated neurons that integrate and communicate by synapses. This opens a possible future scenario of autotransplantation, in which stem cells are harvested from small biopsies of the ventricular wall and propagated in vitro before transplantation.
Moe
Morten C
MC
Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
Westerlund
Ulf
U
Varghese
Mercy
M
Berg-Johnsen
Jon
J
Svensson
Mikael
M
Langmoen
Iver A
IA
D018750:6-Cyano-7-nitroquinoxaline-2,3-dione / Q000494:pharmacology; D000293:Adolescent; D000328:Adult; D000368:Aged; D001921:Brain / Q000166:cytology*; D002118:Calcium / Q000378:metabolism; D002352:Carrier Proteins; D002454:Cell Differentiation / Q000502:physiology*; D002478:Cells, Cultured; D002648:Child; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004307:Dose-Response Relationship, Radiation; D029721:Drosophila Proteins; D004558:Electric Stimulation / Q000379:methods; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005455:Fluorescent Antibody Technique / Q000379:methods; D006801:Humans; D008564:Membrane Potentials / Q000502:physiology / Q000528:radiation effects; D008875:Middle Aged; D009415:Nerve Net / Q000502:physiology*; D009419:Nerve Tissue Proteins; D009474:Neurons / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D018408:Patch-Clamp Techniques / Q000379:methods; D011189:Potassium Chloride / Q000494:pharmacology; D017470:Receptors, Glutamate / Q000378:metabolism; D013234:Stem Cells / Q000502:physiology*; D016708:Synaptophysin / Q000378:metabolism; D013997:Time Factors; D014404:Tubulin / Q000378:metabolism; D050598:Vesicular Glutamate Transport Protein 1 / Q000378:metabolism
D002352:Carrier Proteins; D029721:Drosophila Proteins; D018691:Excitatory Amino Acid Antagonists; D009419:Nerve Tissue Proteins; D017470:Receptors, Glutamate; C493464:SLC17A7 protein, human; D016708:Synaptophysin; D014404:Tubulin; D050598:Vesicular Glutamate Transport Protein 1; C420114:stnB protein, Drosophila; D011189:Potassium Chloride; D016291:Dizocilpine Maleate; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D002118:Calcium