Mutant hypoxia-inducible factor 1α modified bone marrow mesenchymal stem cells ameliorate cerebral ischemia

Cell therapy is the most advanced treatment of the cerebral ischemia, nowadays. Herein, we discuss the neuroprotective effects of bone marrow mesenchymal stem cells (BMSCs) on rat hippocampal cells following intravenous injection of these cells in an ischemia-reperfusion model. Adult male Wistar rats were divided into 5 groups: control, sham (surgery without blockage of common carotid arteries), ischemia (common carotid arteries were blocked for 30 min prior to reperfusion), vehicle (7 days after ischemia PBS was injected via the tail vein), and treatment (injections of BMSC into the tail veins 7 days after ischemia). We performed neuromuscular and vestibulomotor function tests to assess behavioral function and, finally, brains were subjected to hematoxylin and eosin (H&E), anti-Brdu immunohistochemistry, and TUNEL staining. The ischemia group had severe apoptosis. The group treated with BMSCs had a lower mortality rate and also had significant improvement in functional recovery (P<0.001). Ischemia-reperfusion for 30 min causes damage and extensive neuronal death in the hippocampus, especially in CA1 and CA3 regions, leading to several functional and neurological deficits. In conclusion, intravenous injection of BMSCs can significantly decrease the number of apoptotic neurons and significantly improve functional recovery, which may be a beneficial treatment method for ischemic injuries.

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Recovery of neurological function of ischemic stroke by application of conditioned medium of bone marrow mesenchymal stem cells derived from normal and cerebral ischemia rats

Journal of Biomedical Science ◽

10.1186/1423-0127-21-5 ◽

2014 ◽

Vol 21 (1) ◽

pp. 5 ◽

Cited By ~ 52

Author(s):

May-Jywan Tsai ◽

Shen-Kou Tsai ◽

Bo-Ruei Hu ◽

Dann-Ying Liou ◽

Shih-Ling Huang ◽

...

Keyword(s):

Stem Cells ◽

Bone Marrow ◽

Mesenchymal Stem Cells ◽

Ischemic Stroke ◽

Cerebral Ischemia ◽

Conditioned Medium ◽

Neurological Function ◽

Marrow Mesenchymal Stem Cells

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Exosomes derived from bone marrow mesenchymal stem cells promote angiogenesis via transfer of miR-21-5p after cerebral ischemia in mice

10.21203/rs.3.rs-421529/v1 ◽

2021 ◽

Author(s):

Hui Hu ◽

xiaowei Hu ◽

lin Li ◽

Jingjing Gu ◽

Yan Fang ◽

...

Keyword(s):

Stem Cells ◽

Bone Marrow ◽

Mesenchymal Stem Cells ◽

Cerebral Ischemia ◽

Western Blot ◽

Tube Formation ◽

Neurological Function ◽

In Vitro Assays ◽

Marrow Mesenchymal Stem Cells

Abstract Background Mesenchymal stem cells (MSCs) transplantation is a potential clinical therapy for cerebral ischemia. The therapeutic effects of MSCs primarily depends on the paracrine action by releasing exosomes (Exos). Exosomes derived from bone marrow mesenchymal stem cells (BMSC-Exos) could modulate target cell functions by transferring microRNAs (miRs) cargo. In this study, we aimed to investigate whether BMSC-Exos could promote angiogenesis via transfer of miR-21-5p after cerebral ischemia. Methods BMSC-Exos were isolated from conditioned medium of BMSCs by differential ultracentrifugation, and confirmed by transmission electron microscopy, nanoparticle tracking analysis, and western blot analysis. In mice with middle cerebral artery occlusion (MCAO), the neurological function was evaluated by Zea Longa’s method, and the infarct volume and microvessel density were detected by TTC staining and vWF immunofluorescence staining, respectively. The proangiogenic effects of BMSC-Exos were assessed via proliferation, migration, and tube formation of human umbilical vein endothelial cells (HUVECs) in vitro assays. The miR-21-5p expression was detected by qRT-PCR. The expression levels of VEGF, VEGFR2, Ang-1, and Tie-2 were determined by western blot. Results BMSC-Exos significantly improved neurological function and reduced infract volume after cerebral ischemia. Moreover, BMSC-Exos significantly upregulated the microvessel density and the expression levels of proangiogenic proteins VEGF, VEGFR2, Ang-1 and Tie-2 in the ischemic boundary region. MiR-21-5p expression was also dramatically increased after cerebral ischemia. In vitro assays revealed that BMSC-Exos enhanced HUVECs functions including proliferation, migration and tube formation, as well as increasing the expression of VEGF and VEGFR2. However, these proangiogenic effects of BMSC-Exos on HUVECs were reversed by miR-21-5p inhibitor. Conclusion Our study indicated that BMSC-Exos could promote angiogenesis and neurological function recovery via transfer of miR-21-5p. Therefore, the application of miR-21-5p-loaded BMSC-Exos might be an attractive treatment strategy of cerebral ischemia.

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