Human placental derived stem cells protection in stroke injury.

Abstract

Although stroke remains the 2nd leading cause of mortality with disastrous effects on long‐term disability in adults, there are few effective therapeutic approaches which can reduce post‐ischemic brain injury and neurological defects. Recently, stem cell‐based therapies for stroke have been shown to be neuroprotective and neurorestorative. Since stroke is a non‐progressive neurological disease, stem cell therapy would be an ideal approach to limit inflammation, suppress injurious immune mechanisms and stimulation of endogenous repair processes. In this study, we are using placental derived stem cells (hPDSC) as a treatment for brain damage following ischemia/reperfusion. The objective of this study was to determine the therapeutic potential of hPDSC in the treatment of post‐ischemic brain injury after a stroke event. Our central hypothesis is that hPDSC will decrease brain damage following cerebral ischemia/reperfusion by reducing immune system activation and infiltration, oxidative stress, and enhancing survival pathways. We measured infarct size and neurological scores on Sprague‐Dawley rats using a 2h middle cerebral artery occlusion (MCAO) model of stroke injury in adult rats. We found that intra‐arterial administration of hPDSC (1×10^6/0.3 ml) at the time of reperfusion significantly reduced infarct size from 49.8±18.7% (MCAO/HBSS) to 12.9±6.3% (MCAO/hPDSC), p=0.003 (comparing ipsilateral to contralateral hemispheres). Similarly, neurological scores were improved from 12.4±1.51 (MCAO/HBSS) to 18.8±2.48 (MCAO/hPDSC) p=0.0012(Garcia scale). Although the mechanistic basis of protection is still not completely clear, hPDSC improvements seem to reflect sparing of the cortex; less protection appears to be seen in the caudate. This cortical protection was also associated with improvements in tissue histopathology characterized by reduced necrosis and vacuolization with apparent preservation of oligodendrocytes. Our findings demonstrate that acute intra‐arterial administration of hPDSCs during reperfusion can significantly improves stroke outcomes at 24h. Future studies to evaluate timing, cell dosing and the cellular/molecular mechanisms underlying their beneficial actions may even further improve overall outcomes in this form of stem cell therapy. These studies will help fill a void in our understanding of the influence of hPDSC on cerebral blood vessels and how these factors may reduce brain damage following a stroke event.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.