Journal
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH
Volume 1853, Issue 2, Pages 422-430Publisher
ELSEVIER
DOI: 10.1016/j.bbamcr.2014.11.009
Keywords
Conditioned medium; Human placental mesenchymal-like adherent; stromal cells (PLX); IL-6; Ischemia; Neuroprotection; NGF-differentiated PC12 cells; Oxygen and glucose deprivation; Reperfusion; Semaxanib; VEGF
Categories
Funding
- David R. Bloom Center for Pharmacy
- Dr. Adolf and Klara Brettler Center for Research in Molecular Pharmacology and Therapeutics at The Hebrew University of Jerusalem, Israel
- HUJI Intramural Research Funds
- Gulton Foundation NY
- Israel Ministry of Industry and Commerce, Magneton Programs
Ask authors/readers for more resources
Mesenchymal stem cells are potent candidates in stroke therapy due to their ability to secrete protective anti-inflammatory cytokines and growth factors. We investigated the neuroprotective effects of human placental mesenchymal-like adherent stromal cells (PLX) using an established ischemic model of nerve growth factor (NGF)-differentiated pheochromocytoma PC12 cells exposed to oxygen and glucose deprivation (OGD) followed by reperfusion. Under optimal conditions, 2 x 10(5) PLX cells, added in a trans-well system, conferred 30-60% neuroprotection to PC12 cells subjected to ischemic insult. PC12 cell death, measured by LDH release, was reduced by PLX cells or by conditioned medium derived from PLX cells exposed to ischemia, suggesting the active release of factorial components. Since neuroprotection is a prominent function of the cytokine IL-6 and the angiogenic factor VEGF(165), we measured their secretion using selective ELISA of the cells under ischemic or normoxic conditions. IL-6 and VEGF(165) secretion by co-culture of PC12 and PLX cells was significantly higher under ischemic compared to normoxic conditions. Exogenous supplementation of 10 ng/ml each of IL-6 and VEGF(165) to insulted PC12 cells conferred neuroprotection, reminiscent of the neuroprotective effect of PLX cells or their conditioned medium. Growth factors as well as co-culture conditioned medium effects were reduced by 70% and 20% upon pretreatment with 240 ng/ml Semaxanib (anti VEGF(165)) and/or 400 ng/ml neutralizing anti IL-6 antibody, respectively. Therefore, PDC-induced neuroprotection in ischemic PC12 cells may be partially explained by IL-6 and VEGF(165) secretion. These findings may also account for the therapeutic effects seen in clinical trials after treatment with these cells. (C) 2014 Elsevier B.V. All rights reserved.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available