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Helen Lew, Seungsoo Rho, Mira Park; Human Chorionic plate derived mesenchymal stem cells (CPMSC) rescue deterioration of R28 cells exposed to ischemia by expression of GAP-43 and HIF-1α.. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):2257.
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© ARVO (1962-2015); The Authors (2016-present)
Different damage factors are known to promote cell death in optic nerve cells. Mesenchymal stem cells are potent candidates in traumatic optic nerve injury due to their ability to secrete protective anti-inflammatory cytokines and recovery factors. We investigated the neuroprotective effects of human chorionic plate derived mesenchymal stem cells (CPMSC) using an established ischemic model of R28 cells which were subjected to induced inflammation and exposed to hypoxia.
Under optimal conditions, 2×105 CPMSCs, added in a trans-well system, conferred neuroprotection to R28 cells subjected to inflammation insult of TNF-α (10ng/ml) and hypoxic insult of CoCl2 (50µM/ml). R28 cell death, measured by dehydrogenase activities in cells (Cell Counting Kit-8 assay). Since neuroprotection is a prominent function of the cytokine GAP-43 and HIF-1α, we investigated the expression of GAP-43, HIF-1α and activated caspase3 using western blot under injured or control conditions. And the expression was evaluated upon CPMSC co-culture conditioned media as well as pretreatment with GAP-43 antagonist glutamate N-methyl-D-aspartate (NMDA) receptor blockade and HIF-1α antagonist PX478, respectively.
R28 cell death was reduced by CPMSCs or by conditioned medium derived from CPMSCs exposed to inflammation or hypoxia, suggesting the active release of factorial components. GAP-43 protein level was recovered and activated caspase3 were also reduced by co-culture of R28 with CPMSCs under ischemic compared to control conditions.
Therefore, CPMSCs induced neuroprotection in ischemic R28 cells may be partially explained by GAP-43 and HIF-1α expression. These findings may also explain for the therapeutic effects seen in optic nerve injury in vivo studies after treatment with these cells.
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