Abstract Title:

Neuroprotective Effect of Human Placenta-derived Cell Treatment of Stroke in Rats.

Abstract Source:

Cell Transplant. 2012 Mar 28. Epub 2012 Mar 28. PMID: 22469567

Abstract Author(s):

Jieli Chen, Amjad Shehadah, Ajai Pal, Alex Zacharek, Xu Cui, Yishen Cui, Cynthia Roberts, Mei Lu, Andrew Zeitlin, Robert Hariri, Michael Chopp


Background: Human placenta-derived adherent (PDA001) cells are mesenchymal-like stem cells isolated from postpartum human placenta. In this study, we tested whether intravenously-infused PDA001 improves neurological functional recovery after stroke in rats. In addition, potential mechanisms underlying the PDA001-induced neuroprotective effect were investigated.Methods: Young adult male rats (2-3 months) were subjected to 2h of middle cerebral artery occlusion (MCAo) and treated with PDA001 (4x10⁶) or vehicle controls (Dextran vehicle or phosphate buffer saline (PBS)) via intravenous (IV) administration initiated at 4h after MCAo. A battery of functional tests and measurements of lesion volume and apoptotic cells were performed. Immunostaining and ELISA assays for vascular endothelial growth factor (VEGF) and hepatocyte growth factor (HGF) and brain-derived neurotrophic factor (BDNF) were performed in the ischemic brain to test the potential mechanisms underlying the neuroprotective effects of PDA001 cell treatment of stroke.Results: PDA001 cell treatment at 4h post stroke significantly improved functional outcome, and as well as significantly decreased lesion volume, TUNEL and cleaved-Caspase-3 positive cell number in the ischemic brain, compared to MCAo-vehicle and MCAo-PBS control. Treatment of stroke with PDA001 cells also significantly increased HGF and VEGF expression inthe ischemic border zone (IBZ) compared to controls. Using ELISA assays, treatment of stroke with PDA001 cells significantly increased VEGF, HGF and BDNF levels in the ischemic brain compared to controls.Conclusion: When administered intravenously at 4h after MCAo, PDA001 cells promoted neuroprotective effects. These effects induced by PDA001 cell treatment may be related to the increase of VEGF, HGF and BDNF expression and a decrease of apoptosis. PDA001 cells may provide a viable cell source to treat stroke.

Study Type : Animal Study

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