Neural stem cells protect against glutamate-induced excitotoxicity and promote survival of injured motor neurons through the secretion of neurotrophic factors.
Besides their capacity to give rise to neurons and/or glia, neural stem cells (NSCs) appear to inherently secrete neurotrophic factors beneficial to injured neurons. To test this potential, we have implanted NSCs onto or adjacent to spinal cord cultures. When NSCs were placed adjacent to the spinal cord sections, motor neuron axons grew toward the NSCs. Furthermore, conditioned medium from NSCs cultures was also able to induce similar axonal outgrowth, suggesting that these NSCs secrete soluble factors that have tropic and/or trophic properties. ELISA revealed that the NSCs secrete glial cell-line-derived factor (GDNF) and nerve growth factor (NGF). Interestingly, preincubation of the conditioned medium with GDNF-blocking antibodies abolished axonal outgrowth. We also showed that NSCs can protect spinal cord cultures from experimentally induced excitotoxic damage. The neuroprotective potential of NSCs was further confirmed in vivo by their ability to protect against motor neuron cell death.
Lladó
Jerònia
J
Department of Neurology and Neuroscience, Johns Hopkins University, Baltimore, MD 21287, USA.
Haenggeli
Christine
C
Maragakis
Nicholas J
NJ
Snyder
Evan Y
EY
Rothstein
Jeffrey D
JD
D000818:Animals; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D018920:Coculture Techniques; D018690:Excitatory Amino Acid Agonists / Q000633:toxicity; D051100:Glial Cell Line-Derived Neurotrophic Factor; D018698:Glutamic Acid / Q000633:toxicity*; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D009046:Motor Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D009414:Nerve Growth Factors / Q000378:metabolism* / Q000502:physiology; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D018696:Neuroprotective Agents / Q000378:metabolism*; D009924:Organ Culture Techniques; D051381:Rats; D013234:Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*
D018690:Excitatory Amino Acid Agonists; C495039:GDNF protein, human; C495040:Gdnf protein, mouse; C495041:Gdnf protein, rat; D051100:Glial Cell Line-Derived Neurotrophic Factor; D009414:Nerve Growth Factors; D018696:Neuroprotective Agents; D018698:Glutamic Acid