Immunomodulatory effect of CD200-positive human placenta-derived stem cells in the early phase of stroke

Abstract

Human placenta amniotic membrane-derived mesenchymal stem cells (AMSCs) regulate immune responses, and this property can be exploited to treat stroke patients via cell therapy. We investigated the expression profile of AMSCs cultured under hypoxic conditions and observed interesting expression changes in various genes involved in immune regulation. CD200, an anti-inflammatory factor and positive regulator of TGF-β, was more highly expressed under hypoxic conditions than normoxic conditions. Furthermore, AMSCs exhibited inhibition of pro-inflammatory cytokine expression in co-cultures with LPS-primed BV2 microglia, and this effect was decreased in CD200-silenced AMSCs. The AMSCs transplanted into the ischemic rat model of stroke dramatically inhibited the expression of pro-inflammatory cytokines and up-regulated CD200, as compared with the levels in the sham-treated group. Moreover, decreased microglia activation in the boundary region and improvements in behavior were confirmed in AMSC-treated ischemic rats. The results suggested that the highly expressed CD200 from the AMSCs in a hypoxic environment modulates levels of inflammatory cytokines and microglial activation, thus increasing the therapeutic recovery potential after hypoxic-ischemic brain injury, and further demonstrated the immunomodulatory function of AMSCs in a stroke model.

Bidirectional Microglia–Neuron Communication in Health and Disease

“…Injection of recombinant CD200 intracerebroventricular, performed right after pMCAO induction, reduced microglial activation and expression of cytokine TNF, IL-1β, and IL-10 ( Yang et al, 2018b ). To be able to use the beneficial effect of CD200 signaling in ischemic stroke, Kong et al (2018) used human mesenchymal stem cells with high CD200 expression from human placenta which they transplanted intracerebrally 24 h after transient middle cerebral artery occlusion (tMCAO). Interestingly, they report reduced microglia activation in the infarct boundary area, smaller infarct and improved behavior.…”

“…Interestingly, they report reduced microglia activation in the infarct boundary area, smaller infarct and improved behavior. Silencing of CD200 in the mesenchymal stem cells also reduced the inflammatory response in BV2 microglia when applying a co-culture system ( Kong et al, 2018 ). Using a similar rat stroke model, Matsumoto et al (2015) investigated if the CD200 could be used to distinguish M1 or M2 macrophage/microglia in the infarct at 7 days after ischemia, but were not able to make this distinction in M1/M2 based on CD200 expression.…”

Progesterone Prolongs Viability and Anti-inflammatory Functions of Explanted Preterm Ovine Amniotic Membrane

“…It has been demonstrated that the AM increases its immunomodulatory and anti-inflammatory properties upon an inflammatory stimulus, which is likely to prevent the risk of a premature abortion (Flores-Espinosa et al, 2014). Likewise, AECs and AMSCs also show an increase in their native immunomodulatory properties by secreting high levels of antiinflammatory cytokines when stimulated with bacterial LPS (Canciello et al, 2017;Kong et al, 2018). In the present study, it was not possible to distinguish between the contribution of the two AM cell types (AECs and AMSCs) even if, considering the prevalence of AECs in the AM structure, it would be wise to think that the increase in anti-inflammatory cytokines' mRNA expression and releases recorded after LPS stimulation may be mainly attributable to the epithelial layer.…”

Bioassay for monitoring the anti-aging effect of cord blood treatment

“…We modified the Rotarod test of Kong et al 30 to assess locomotor coordination. The rotarod with a 3-cm diameter rod started at 4 rpm and accelerated by 4 rpm per 30 seconds for 5 min.…”