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

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Abstract

Stroke remains a highly 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 require further identification. 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 sacrificed, 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 significantly 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 significantly 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-inflammatory 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.

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Acknowledgements

We gratefully acknowledge the support from the Dalian Institute of Chemical Physics, Chinese Academy of Sciences. We thank Wang XL and Wang XH for their excellent technical assistance.

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Author notes

  1. Xia Xiao and Ya-Nan Liu contributed equally to this work.

Authors and Affiliations

  1. Department of Neurology, The Second Hospital of Dalian Medical University, 467 Zhongshan Road, Shahekou District, Dalian, 116000, Liaoning, China

    Qian Wang & Yun-Xia Du

  2. Department of Neurology, Xuanwu Hospital, Capital Medical University, 45 Changchun Road, Xicheng District, Beijing, 100053, China

    Shu-Fang Zhao

  3. Department of Emergency Intensive Care Unit, The Second Hospital of Dalian Medical University, 467 Zhongshan Road, Shahekou District, Dalian, 116000, Liaoning, China

    Xia Xiao

  4. Department of Geriatrics, The Second Hospital of Dalian Medical University, 467 Zhongshan Road, Shahekou District, Dalian, 116000, Liaoning, China

    Ya-Nan Liu

  5. Department of Histoembryology, College of Basic Medical Sciences, Dalian Medical University, 9 West Section, Lvshunnan Road, Lvshunkou District, Dalian, 116044, Liaoning, China

    Xiu-Li Wang

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  1. Qian Wang
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The authors contributed equally.

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Correspondence to Qian Wang or Shu-Fang Zhao.

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All procedures performed in studies involving animals were in accordance with the ethical standards of the UK Animals Act. This article does not contain any studies with human participants performed by any of the authors.

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Wang, Q., Zhao, SF., Xiao, X. et al. Combined Treatment of Bone Marrow Mesenchymal Stem Cells and Fasudil Promotes Neurovascular Remodeling and Neurological Function Recovery in Ischemic Stroke. Appl Biochem Biotechnol 194, 801–812 (2022). https://doi.org/10.1007/s12010-021-03679-6

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  • DOI: https://doi.org/10.1007/s12010-021-03679-6

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