Human Umbilical Cord Blood Cells Protect Oligodendrocytes from Brain Ischemia through Akt Signal Transduction

Abstract

Background: Human umbilical cord blood cells are an effective experimental treatment for stroke. Results: These cells activate Akt to increase peroxiredoxin 4 and are essential for oligodendrocyte survival during ischemia. Conclusion: Akt and peroxiredoxin 4 are key molecules in transducing the cellular protection elicited by cord blood cells. Significance: Identifying this signaling pathway provides new pharmaceutical targets for stroke treatment.

Enhancing endogenous capacity to repair a stroke-damaged brain: An evolving field for stroke research

“…Further, the total redox potential (anti-oxidant activity) was attributable to the HUCB cells. It is not surprising, therefore, that HUCB MNCs increase gene and protein expression of multiple anti-oxidant enzymes in both neurons and oligodendrocytes in vitro and in vivo (Rowe et al, 2010; Rowe et al, 2012). Bone marrow-derived MSCs have similar effects to those observed with HUCB MNCs, decreasing both oxidative stress and lipid peroxidation (Calio et al, 2014).…”

“…NSCs increase BDNF, TGF-β1, SDF-1α, VEGF and insulin-like growth factor — 1 in the ischemic mouse brain (Capone et al, 2007). HUCB MNCs activate the cell survival/neuroprotective Akt signaling pathway in both neurons (Shahaduzzaman et al, 2015) and oligodendrocytes (Rowe et al, 2012). This pathway is linked to increased expression of antioxidant enzymes and decreased pro-inflammatory mediators (Rowe et al, 2010; Shahaduzzaman et al, 2015).…”

The role of the leukemia inhibitory factor receptor in neuroprotective signaling

“…The activation of this receptor relays intracellular signals that result in enhanced cellular survival in neural cells and altering the phenotype of T cells and macrophages from an inflammatory to an anti-inflammatory one. In brain injury, such as stroke, neural cell survival signaling is necessary to protect cells (Rowe et al, 2012). Additionally, the immune system, which mounts an inflammatory neurodegenerative response to the brain injury, needs to be diverted towards an anti-inflammatory state (Ajmo et al, 2008; Offner et al, 2006).…”

Cord Blood as a Treatment for Stroke

“…However, when the cells were administered at 48-h post-MCAO, IV cell transplants only required 10 6 cells (Newcomb et al 2006). When UCB cell doses of 1 × 10 6 cells are administered at 48-h post-MCAO they consistently improve function and reduce neural injury (Rowe et al 2012). Examining tissue for phosphorylated (p)Akt, a protein involved in cell survival pathways, within white matter of stroked brains, investigators found that UCB cell treatment increased ipsilateral pAkt expression at 72 and 96 h postischemia.…”

“…Further studies using microarray and quantitative real time polymerase chain reaction (qRT-PCR) assays demonstrated that soluble factors secreted by the UCB cells increased expression of oligodendrocyte repair, proliferation, and survival genes Insig1, Mt3, Prdx4, Stmn2, MOG, and Vcan (Rowe et al 2010). These UCB effects were mediated by Akt signal transduction pathways, since addition of an Akt inhibitor to the culture medium eliminated the effects of the UCB cells (Rowe et al 2012); UCB induced peroxiredoxin 4 (Prdx4) expression. Prdx4 expression, an endogenous antioxidant often involved in the reduction of oxidative stress, was prevented when Akt was inhibited.…”