Human umbilical cord mesenchymal stem cells protect against ischemic brain injury in mouse by regulating peripheral immunoinflammation

• hUC-MSCs have neuroprotection from MCAO-induced ischemic injury;
• hUC-MSCs reduce peripheral and neuronal inflammation;
• hUC-MSCs shift the Th17/Treg differentiation from Naïve CD4+ T cells;
• hUC-MSCs modulate the differentiation of Th17/Treg through TGF-β.

Current treatments for ischemic stroke are limited, stem cell transplantation offers great potential as a therapeutic strategy. The present study was undertaken to determine whether human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) could improve brain injury after middle cerebral artery occlusion (MCAO) through modulating peripheral immunoinflammation. The study showed that neurological deficit was ameliorated and brain edema, infarct volume was significantly decreased from 72 h to 1 week post-MCAO with hUC-MSCs treatment via tail vein injection within 30 mins after stroke; hUC-MSCs attenuated the levels of inflammatory factors including IL-1, TNF-α, IL-23, IL-17 and IL-10 in peripheral blood serum and ischemia hemisphere after stroke; hUC-MSCs significantly decreased the level of Th17 cells at 24 h and increased the level of Tregs at 72 h post-MCAO in peripheral immune system; the level of TGF-β in blood serum was enhanced by hUC-MSCs. In conclusion, our findings suggested that hUC-MSCs had neuroprotection in MCAO mice by TGF-β modulating peripheral immune and hUC-MSCs may be as a potential therapy for ischemic stroke.