Effects of Bone Marrow-Derived Mesenchymal Stem Cells on the Axonal Outgrowth through Activation of PI3K-AKT Signaling in Primary Cortical Neurons Followed Oxygen-Glucose Deprivation InjuryReportar como inadecuado




Effects of Bone Marrow-Derived Mesenchymal Stem Cells on the Axonal Outgrowth through Activation of PI3K-AKT Signaling in Primary Cortical Neurons Followed Oxygen-Glucose Deprivation Injury - Descarga este documento en PDF. Documentación en PDF para descargar gratis. Disponible también para leer online.

Background

Transplantation with bone marrow-derived mesenchymal stem cells BMSCs improves the survival of neurons and axonal outgrowth after stroke remains undetermined. Here, we investigated whether PI3K-AKT signaling pathway is involved in these therapeutic effects of BMSCs.

Methodology-Principal Findings

1 BMSCs and cortical neurons were derived from Sprague-Dawley rats. The injured neurons were induced by Oxygen–Glucose Deprivation OGD, and then were respectively co-cultured for 48 hours with BMSCs at different densities 5×103, 5×105-ml in transwell co-culture system. The average length of axon and expression of GAP-43 were examined to assess the effect of BMSCs on axonal outgrowth after the damage of neurons induced by OGD. 2 The injured neurons were cultured with a conditioned medium CM of BMSCs cultured for 24 hours in neurobasal medium. During the process, we further identified whether PI3K-AKT signaling pathway is involved through the adjunction of LY294002 a specific phosphatidylinositide-3-kinase PI3K inhibitor. Two hours later, the expression of pAKT phosphorylated AKT and AKT were analyzed by Western blotting. The length of axons, the expression of GAP-43 and the survival of neurons were measured at 48 hours.

Results

Both BMSCs and CM from BMSCs inreased the axonal length and GAP-43 expression in OGD-injured cortical neurons. There was no difference between the effects of BMSCs of 5×105-ml and of 5×103-ml on axonal outgrowth. Expression of pAKT enhanced significantly at 2 hours and the neuron survival increased at 48 hours after the injured neurons cultured with the CM, respectively. These effects of CM were prevented by inhibitor LY294002.

Conclusions-Significance

BMSCs promote axonal outgrowth and the survival of neurons against the damage from OGD in vitro by the paracrine effects through PI3K-AKT signaling pathway.



Autor: Yong Liu, Yixian Zhang, Longzai Lin, Feifei Lin, Tin Li, Houwei Du, Ronghua Chen, Wei Zheng, Nan Liu

Fuente: http://plos.srce.hr/



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