Hyperthermia-conditioned OECs serum-free-conditioned medium induce NSC differentiation into neuron more efficiently by the upregulation of HIF-1 alpha and binding activity.
BACKGROUND
Recent studies provide solid evidence for the importance to delineate the combined transplantation of neural stem cells (NSCs) and olfactory ensheathing cells (OECs) for the repair of central nervous system injury. One of the limitations of this approach is that the proportion of neurons differentiated from NSCs still remains at low level. Thus, how to induce NSCs to differentiate into neurons more efficiently by OECs is an attractive problem, which needs attention to be resolved. In the present study, we investigated the effects of hyperthermia-conditioned OEC-conditioned medium (OCM) on induction of NSCs into nerve cells.


METHODS
The conditioned medium, named 37OCM, 40OCM, and 40OCM+R (treated with HIF-1a inhibitor), were collected after OECs had been incubated at 37°C or 40°C for 6 hr, followed by incubation at 37°C for 42 hr; then, these conditioned medium were collected and used for NSC induction.


RESULTS
Results of the present study demonstrated for the first time that 6 hr of hyperthermia (40°C) could induce OECs upregulation and the expression of hypoxia-inducible factor-1 alpha (HIF-1α). Moreover, compared with 37OCM and 40OCM+R, 40OCM could induce NSCs differentiation into neurons more efficiently, and this phenomenon is associated with the upregulation of HIF-1α after hyperthermia conditioning.


CONCLUSIONS
The data implied that the secretory protein in OECs-cultured medium and upregulation of HIF-1α expression and binding activity induced by hyperthermia-conditioned OECs have synergistic effect to induce NSCs differentiation into a neural lineage.
1 Department of Neurosurgery, the Second Affiliated Hospital of Hunan Normal University (PLA 163 Hospital), Changsha, People's Republic of China. 2 Key Laboratory of Protein Chemistry and Developmental Biology of Education Committee, College of Life Sciences, Hunan Normal University, Changsha, People's Republic of China. 3 Address correspondence to: Ming Lu, M.D., Department of Neurosurgery, the Second Affiliated Hospital of Hunan Normal University (PLA 163 Hospital), Changsha 410003, People's Republic of China; Ping Chen, Ph.D., Key Laboratory of Protein Chemistry and Developmental Biology of Education Committee, College of Life Sciences, Hunan Normal University, Changsha 410081, P.R. China.
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D000818:Animals; D002460:Cell Line; D002470:Cell Survival; D017077:Culture Media, Conditioned / Q000378:metabolism*; D016895:Culture Media, Serum-Free / Q000378:metabolism*; D006979:Hyperthermia, Induced; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism*; D051379:Mice; D058953:Neural Stem Cells / Q000378:metabolism*; D055495:Neurogenesis; D009474:Neurons / Q000378:metabolism*; D009830:Olfactory Bulb / Q000166:cytology / Q000378:metabolism*; D019899:Paracrine Communication; D011485:Protein Binding; D013997:Time Factors; D015854:Up-Regulation
D017077:Culture Media, Conditioned; D016895:Culture Media, Serum-Free; C497443:Hif1a protein, mouse; D051795:Hypoxia-Inducible Factor 1, alpha Subunit