Therapeutic Potential of a Combination of Electroacupuncture and Human iPSC-Derived Small Extracellular Vesicles for Ischemic Stroke

Abstract

This paper aimed to explore the roles of the combination of electroacupuncture (EA) and induced pluripotent stem cell-derived small extracellular vesicles (iPSC-EVs) on mice with ischemic stroke and the underlying mechanisms. A focal cerebral ischemia model was established in C57BL/6 mice through middle cerebral artery occlusion (MCAO). After 3 days, neurological impairment and motor function were examined by performing behavioral tests. The infarct volume and neuronal apoptosis were examined using TTC staining and TUNEL assays. Flow cytometry was performed to assess the proliferation of T lymphocytes. The changes in the interleukin (IL)-33/ST2 axis were evaluated by immunofluorescence and Western blotting. The combination of EA and iPSC-EVs treatment ameliorated neurological impairments and reduced the infarct volume and neuronal apoptosis in MCAO mice. EA plus iPSC-EVs suppressed T helper (Th1) and Th17 responses and promoted the regulatory T cell (Treg) response. In addition, EA plus iPSC-EVs exerted neuroprotective effects by regulating the IL-33/ST2 axis and inhibiting the microglia and astrocyte activation. Taken together, the study shows that EA and iPSC-EVs exerted a synergistic neuroprotective effect in MCAO mice, and this treatment may represent a novel potent therapy for ischemic stroke and damage to other tissues.

Acupuncture at GV20 and ST36 Improves the Recovery of Behavioral Activity in Rats Subjected to Cerebral Ischemia/Reperfusion Injury

“…ST36 belongs to the stomach meridian, which is rich in both qi and blood. Thus, it is considered an acupuncture point that plays a role in the recovery of paralysis ( Cui et al, 2021 ; Deng et al, 2022 ). The combined use of these two acupuncture points is effective at dredging channels and collaterals, modifying the blood and qi , and balancing yin and yang .…”

“…Electroacupuncture therapy was developed from traditional acupuncture, adding electrical stimulation to acupuncture therapy. Many studies have focused on mechanisms underlying the neuroprotective effect of electroacupuncture therapy, and some have shown that electroacupuncture improves neurological behavioral outcomes ( Deng et al, 2022 ), increases cerebral blood flow in the ischemic area ( Mei et al, 2020 ), inhibits neural inflammation and neural hypoxia ( Xu et al, 2018 ; Long et al, 2019 ), and promotes angiogenesis and neurogenesis ( Shi et al, 2017 ; Chen et al, 2020 ; Li et al, 2020 , 2021 ). Therefore, we selected GV20 and the left ST36 to treat the hemiplegia caused by CIRI in the rats.…”

“…Electroacupuncture (EA) is a complementary combination therapy consisting of traditional acupuncture and electrical stimulation. EA treatment effectively attenuates inflammatory injury and exerts a neuroprotective effect on ischemic stroke ( Deng et al, 2022 ). We reported that EA treatment at the “Baihui” (GV20) and “Zusanli” (ST36) acupoints alleviated neuronal injury and reduced the infarct volume in rats with CIRI ( Wang et al, 2019 ; Chen et al, 2020 ; Zhang Y. M. et al, 2021 ).…”

Gut microbiota in ischemic stroke: Where we stand and challenges ahead

“…A clinical study found that total BAs levels were inversely associated with 3-month mortality in patients with acute IS (130). The reason may be partly associated with immunity because the imbalance of Th17/Treg was reported to aggravate IS (131), while BAs could control the host immune response by directly regulating the balance of the Th17/Treg (132, 133). Studies have shown that gut microbiota could affect the occurrence and development of IS via metabolizing primary BAs produced by the liver to secondary BAs by Bacteroides, Eubacterium, and Clostridium spp.…”

Interleukin-33 regulates the functional state of microglia

“…WIN 55,212-2 (an agonist for cannabinoid receptors) both promotes IL-33 production and inhibits microglial activation induced by carbon monoxide poisoning ( Du et al, 2020 ). Electroacupuncture combined with induced pluripotent stem cell-derived small extracellular vesicles induces neuroprotection in ischemic stroke through downregulation of the IL-33/ST2 axis and reduction of microglial activation ( Deng et al, 2022 ). These findings indicate a potential role for IL-33 in the stimulation of microglia, but the exact causal role remains unresolved.…”