Murine brain progenitor cells have the ability to differentiate into functional neurons and integrate into the CNS.
Although neural stem and progenitor cells have been shown to differentiate into neurons, few studies have examined the physiological properties of the differentiated neurons derived from stem cells. Here we show that mouse brain progenitor cells (mBPCs) differentiated in culture by removal of mitogenic factors or addition of BDNF or GDNF express neuronal-specific proteins including MAP-2 and synaptobrevin II. However, these cells demonstrate small voltage-gated Na+ currents and are not able to generate action potentials. When the mBPCs are cocultured with developing rat hippocampal neurons, the stem cells differentiate into neurons expressing MAP-2, develop large voltage-gated Na+ currents, and are able to generate action potentials. To investigate the influence of a mature CNS environment on survival, differentiation, migration, and morphological integration, mBPCs were transplanted into the spinal cord of adult mice. Undifferentiated cells transplanted into the spinal cord exhibited limited migration and expressed NG2, but did not differentiate to express MAP-2. Predifferentiated cells migrated to both gray and white matter with about 23% cells developing MAP-2 immunoreactivity after 8 weeks. These results suggest that both the environment and state of differentiation may dictate migration and the differentiation pathway of stem cells after transplantation.
Ding
Shinghua
S
Department of Neuroscience, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA. sding@mail.med.upenn.edu
Messam
Conrad A
CA
Li
Peiying
P
Selzer
Michael E
ME
Dichter
Marc A
MA
Haydon
Philip G
PG
D000200:Action Potentials / Q000502:physiology; D000818:Animals; D001253:Astrocytes / Q000166:cytology / Q000378:metabolism; D001921:Brain / Q000166:cytology* / Q000378:metabolism; D019208:Brain-Derived Neurotrophic Factor / Q000494:pharmacology; D018929:Cell Culture Techniques; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D002490:Central Nervous System / Q000166:cytology* / Q000378:metabolism; D004594:Electrophysiology; D004815:Epidermal Growth Factor / Q000378:metabolism; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology; D005346:Fibroblast Growth Factors / Q000378:metabolism; D051100:Glial Cell Line-Derived Neurotrophic Factor / Q000494:pharmacology; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000166:cytology* / Q000378:metabolism / Q000502:physiology; D013116:Spinal Cord / Q000166:cytology / Q000378:metabolism / Q000601:surgery; D033581:Stem Cell Transplantation / Q000379:methods; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism / Q000502:physiology
D019208:Brain-Derived Neurotrophic Factor; D051100:Glial Cell Line-Derived Neurotrophic Factor; D005904:Glial Fibrillary Acidic Protein; D016222:Fibroblast Growth Factor 2; D005346:Fibroblast Growth Factors; D004815:Epidermal Growth Factor