Mesenchymal Stem Cells Derived from Embryonic Stem Cell -Conditioned Medium Facilitates Neuroprotection Through Enhancement of Neurogenesis on Ischemic Stroke Model

Background: Mesenchymal stem cells have emerged as a potential therapy for a range of neural insults. Although low survival rates and potential tumorigenicity of implanted cells could reduce the efficacy of cell-based treatment, recent inves-tigations have proven that use of stem cell conditioned medium (CM) may be a feasible approach to overcome these limitations. There are numerous cytokines and growth factors in the CM of various stem cells responsible for paracrine protective effects of stem cells. The neurogenesis is crucial for the recovery of neural functions after stroke. The purpose of the present study was to assess the effect of conditioned medium of mesenchymal stem cells on neurological functions, infarct volume and neuro-genesis in ischemic stroke rats.Materials and Methods: Ischemic stroke was induced by standard right middle cerebral artery occlusion method (MCAO) in 8-week old Wistar male rats. Injection of the CM or DMEM (5µl) was respectively done into the left lateral ven-tricle of treatment and control animals from one hour follow-ing the surgery to the second day after MCAO induction (three doses). Behavioral tests were performed on 1, 3 and 7 days after injury. Infarct volumes were evaluated on 3 and 7 days after the MCAO. The expression of Nestin, Ki-67 and Doublecor-tin mRNAs and proteins in the subventricular zone (SVZ) and subgranular zone (SGZ) regions was assessed using Real-time PCR and immunolabeling at 7 days after MCAO.Results: Our results indicated that 90 minutes occlusion of the artery caused impairments in sensory-motor functions in is-chemic rats. Furthermore, i.c.v injection of the CM improved functional recovery in treatment group after stroke. Volume analysis revealed that animals subjected to treatment with CM had significantly smaller infarcts than controls. Treatment with CM significantly increased number of Nestin, Ki-67 and Dou-blecortin-positive cells in ipsilateral hemisphere on the 7th day. Conclusion: Our data suggest that conditioned medium of mes-enchymal stem cells contributes to neuroprotection following a cerebral ischemia insult through an improvement in neurogenesis.

Keywords:

Conditioned Medium , Ischemic Stroke , Neurological Function , Infarct Volume , Neurogenesis