Neuroprotective Effect of Human Placenta-Derived Cell Treatment of Stroke in Rats

Abstract

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. Young adult male rats (2-3 months) were subjected to 2 h of middle cerebral artery occlusion (MCAo) and treated with PDA001 (4 ´ 10 6) or vehicle controls [dextran vehicle or phosphate buffer saline (PBS)] via intravenous (IV) administration initiated at 4 h 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 brainderived neurotrophic factor (BDNF) were performed in the ischemic brain to test the potential mechanisms underlying the neuroprotective effects of PDA001 cell treatment of stroke. PDA001 cell treatment at 4 h poststroke significantly improved functional outcome and 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 in the 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 4 h 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.

Stem cell therapy for abrogating stroke-induced neuroinflammation and relevant secondary cell death mechanisms

“…BM-MSCs exhibit significant immunomodulatory effects in vivo , modulating T-cell proliferation rates, activating a T-regulatory cell phenotype (CD8 + CD28 − Treg), and producing a general suppressive effect on CD4+ and CD8+ T cells (Castro-Manrreza and Montesinos, 2015, Liu et al, 2015). BM-MSC transplantation reduces levels of pro-inflammatory cytokines, including interleukin(IL)-1β and IL-6, upregulates the expression of anti-inflammatory cytokines, such as IL-4, IL-10, and transforming growth factor-β1, and lessens the number of activated microglia in ischemic tissue (Chen et al, 2013; McGuckin et al, 2013; Castro-Manrreza and Montesinos, 2015; Laranjeira et al, 2015). …”

Immune System Involvement in the Degeneration, Neuroprotection, and Restoration after Stroke

“…Results show an increase in functional recovery -and 14 days post-ischemia, as well as an increase level of "DNF, vascular endothelial growth factor VEGF which is an angiogenic factor, increases axonal outgrowth, stop apoptosis and increases neurogenesis, and hepatocyte growth factor HGF which is also angiogenic, and decreased TUNEL and cleaved caspase 3, showing a decreased infarct volume. "lthough not many cells survived until day 14, beneicial efects were still observed [118] Most preclinical investigations focus on delivering treatment in the irst hour after reperfusion and happen in strictly controlled environments, which is why they have shown beneicial efects. Lack of results in clinical trials is atributed to uncontrolled real life setings, diferent populations, comorbidity existence, diferent ischemic territories, duration of occlusion before reperfusion, and a single target for treatment, leaving behind other neural components that might aid recovery.…”

Putative Prophylaxes Updated of Placenta Extract and Aloe vera as Biogenic Stimulants

“…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 [32] .…”