Placental Cells Secrete Factors That Protect Nerves from Ischemic Damage

Cells derived from placenta have been found to protect PC12 cells—rat-derived cells that behave similarly to and are used as stand-ins to study human nerve cells—in a culture-based ischemic stroke model.

The placenta contains mesenchymal-like adherent stromal cells, which are known to have significant therapeutic potential. These cells are thought to promote tissue repair by secreting biologically active substances including cytokines that modulate immune response and factors that enhance the growth of blood vessels.

The Israeli biotechnology company Pluristem Therapeutics (Haifa, Israel) utilizes placental cells obtained following scheduled caesarean section births. These cells are expanded in the company's state-of-the-art manufacturing facility following current Good Manufacturing Practices in proprietary bioreactor systems that create a three-dimensional microenvironment. This three-dimensional technology allows for the controlled, large-scale growth of cells implementing an optimized, standardized, scaled-up and fully automated operation. This procedure enables mass-production of PLacental eXpanded (PLX) cells with batch-to-batch consistency for a fraction of the cost of traditionally expanding cells using culture dishes.

Investigators from Pluristem in cooperation with colleagues from the Hebrew University of Jerusalem (Israel) and The Weizmann Institute of Science (Rehovot, Israel) investigated the neuroprotective effects of PLX cells using an established ischemic model of nerve growth factor (NGF)-differentiated PC12 cells exposed to oxygen and glucose deprivation followed by reperfusion.

They reported in the February 2015 online issue of the journal Biochimica et Biophysica Acta - Molecular Cell Research that under optimal conditions, 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 (lactate dehydrogenase) 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, the investigators measured their secretion using selective ELISAs of the cells under ischemic or normal oxygenation conditions. IL-6 and VEGF165 secretion by co-culture of PC12 and PLX cells was significantly higher under ischemic compared to normal oxygenation conditions. Furthermore, exogenous supplementation of IL-6 and VEGF165 to insulted PC12 cells conferred neuroprotection, reminiscent of the neuroprotective effect of PLX cells or their conditioned medium.

“These latest findings also call to mind two earlier preclinical studies,” said Zami Aberman, CEO of Pluristem Therapeutics, “which indicated that PLX cells may be an effective treatment for both neuropathic and inflammatory nerve pain, suggesting that PLX cells could be a potential treatment for chronic nerve pain resulting from conditions such as diabetic neuropathy.”

Related Links:
Pluristem Therapeutics 
The Hebrew University of Jerusalem
The Weizmann Institute of Science