Pre-differentiated embryonic stem cells promote neuronal regeneration by cross-coupling of BDNF and IL-6 signaling pathways in the host tissue.
The mechanism of embryonic stem (ES) cell therapeutic action remains far from being elucidated. Our recent report has shown that transplantation of ES cells, predifferentiated into neuronal progenitors, prevented appearance of chronic pain behaviors in mice after experimentally induced spinal cord injury. In the current study, we tested the hypothesis that this beneficial effect is mediated by antiapoptotic and regenerative signaling pathways activated in the host tissue by transplanted ES cells. Spinal cord injury was induced by unilateral microinjections of quisqualic acid at spinal levels T12-L2. At 1 week after injury, the pre-differentiated towards neuronal phenotype ES cells were transplanted into the site of injury. Here we show that transplantation of pre-differentiated ES cells activate both brain-derived neurotrophic factor (BDNF) and interleukin-6 (IL-6) signaling pathways in the host tissue, leading to activation of cAMP/PKA, phosporylation of cofilin and synapsin I, and promoting regenerative growth and neuronal survival.
Glazova
Margarita
M
Department of Physiology, The Brody School of Medicine, East Carolina University, Greenville, North Carolina 27834, USA.
Pak
Elena S
ES
Moretto
Justin
J
Hollis
Sarah
S
Brewer
Kori L
KL
Murashov
Alexander K
AK
D000704:Analysis of Variance; D000818:Animals; D015153:Blotting, Western; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism*; D002478:Cells, Cultured; D051338:Cofilin 1 / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism; D053595:Embryonic Stem Cells; D004797:Enzyme-Linked Immunosorbent Assay; D007118:Immunoassay; D007150:Immunohistochemistry; D015850:Interleukin-6 / Q000378:metabolism*; D008159:Lumbar Vertebrae; D008297:Male; D051379:Mice; D009474:Neurons / Q000502:physiology*; D010766:Phosphorylation; D012038:Regeneration / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000502:physiology; D013116:Spinal Cord / Q000378:metabolism / Q000503:physiopathology*; D013119:Spinal Cord Injuries / Q000378:metabolism / Q000503:physiopathology; D033581:Stem Cell Transplantation; D016704:Synapsins / Q000378:metabolism; D013904:Thoracic Vertebrae
D019208:Brain-Derived Neurotrophic Factor; D051338:Cofilin 1; D015850:Interleukin-6; D016704:Synapsins; D000242:Cyclic AMP