Human PLacental eXpanded (PLX) mesenchymal-like adherent stromal cells confer neuroprotection to nerve growth factor (NGF)-differentiated PC12 cells exposed to ischemia by secretion of IL-6 and VEGF

Adi Lahiani, Efrat Zahavi, Nir Netzer, Racheli Ofir, Lena Pinzur, Shani Raveh, Hadar Arien-Zakay, Ephraim Yavin*, Philip Lazarovici

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

30 Scopus citations

Abstract

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, 2×105 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 VEGF165, we measured their secretion using selective ELISA of the cells under ischemic or normoxic conditions. IL-6 and VEGF165 secretion by co-culture of PC12 and PLX cells was significantly higher under ischemic compared to normoxic conditions. Exogenous supplementation of 10ng/ml each of IL-6 and VEGF165 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 240ng/ml Semaxanib (anti VEGF165) and/or 400ng/ml neutralizing anti IL-6 antibody, respectively. Therefore, PLX-induced neuroprotection in ischemic PC12 cells may be partially explained by IL-6 and VEGF165 secretion. These findings may also account for the therapeutic effects seen in clinical trials after treatment with these cells.

Original languageAmerican English
Pages (from-to)422-430
Number of pages9
JournalBiochimica et Biophysica Acta - Molecular Cell Research
Volume1853
Issue number2
DOIs
StatePublished - 1 Feb 2015

Bibliographical note

Publisher Copyright:
© 2014.

Keywords

  • Conditioned medium
  • Human placental mesenchymal-like adherent stromal cells (PLX)
  • IL-6
  • Ischemia
  • NGF-differentiated PC12 cells
  • Neuroprotection
  • Oxygen and glucose deprivation
  • Reperfusion
  • Semaxanib
  • VEGF

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