Combined Treatment of Bone Marrow Mesenchymal Stem Cells and Fasudil Promotes Neurovascular Remodeling and Neurological Function Recovery in Ischemic Stroke

Abstract

Stroke remains a deadly and disabling disease with limited treatment tragedies due to the limitations of available treatments; novel therapies for stroke are needed. In this article, the synergistic results of dual bone marrow mesenchymal stem cells (BMSC) and fasudil treatment in rat models of ischemic stroke still requires further identi cation. Sprague-Dawley rats were used to construct the middle cerebral artery, occlusion models. BMSCs were incubated with fasudil, and MTT was performed to evaluate cell proliferation. The rats were treated with fasudil+BMSC, BMSC, fasudil, and saline. Blood samples were collected for complete blood count analysis and measurement of serum TNF-α levels. The neurological functions were evaluated. After the rats were sacri ced, immunohistochemical staining and TTC staining was performed. Fasudil promoted the proliferation of BMSCs and induced their differentiation into neuron-like cells. BMSCs increased the proportion of neutrophils; nevertheless, fasudil counteracted the neutrophil increase. The TUJ-1/MAP2/VIII factor expression in the fasudil+BMSC group was signi cantly higher than that in the other groups. The number of GFAP-positive cells decreased in the fasudil+BMSC and BMSC alone groups. The infarct volume in the fasudil+BMSC and BMSC alone groups was signi cantly lower than in the fasudil alone and control groups.Both BMSCs and fasudil exert neurorestorative effects in rat models of cerebral ischemia. Fasudil neutralizes the pro-in ammatory effects of BMSCs, while BMSCs and fasudil together had synergistic effects promoting neurovascular remodeling and neurological function recovery in stroke. A combination of BMSCs and fasudil provides a promising method for the treatment of ischemic stroke.

Efficacy and safety of mesenchymal stem cells in patients with acute ischemic stroke: a meta-analysis

“…In this study, mesenchymal stem cell transplantation can improve the neurological deficits in ischemic stroke patients to a certain extent. Studies have shown that the therapeutic mechanism of MSCs mainly involves several aspects: (1) immune regulation: Transplanted MSCs mediate immunosuppression, regulate the activation of inflammatory cytokines and microglia through CD200, an anti-inflammatory cytokine overexpressed by stem cells in hypoxic environments, and reduce the number of microglia/macrophages [ 30 – 32 ]. Or induce microglia to become M2-type polarized, which inhibits inflammatory response, so as to reduce nerve damage in stroke rats [ 32 , 33 ].…”

“…Studies have shown that the therapeutic mechanism of MSCs mainly involves several aspects: (1) immune regulation: Transplanted MSCs mediate immunosuppression, regulate the activation of inflammatory cytokines and microglia through CD200, an anti-inflammatory cytokine overexpressed by stem cells in hypoxic environments, and reduce the number of microglia/macrophages [ 30 – 32 ]. Or induce microglia to become M2-type polarized, which inhibits inflammatory response, so as to reduce nerve damage in stroke rats [ 32 , 33 ]. (2) Apoptosis: calcineurin IS a kind of threonine/phosphatase, which plays an important role in neurohomeostasis.…”