Safety intraparenchymal injection of allogenic placenta mesenchymal stem cells derived exosome in patients underwent decompressive craniectomy following malignant middle cerebral artery infarct, a randomized clinical trial

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Author(s):  
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A. Khojasteh ◽  
M. Soleimani ◽  
S. Oraee Yazdani
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Kyung Sil Jin ◽  
Oh Young Bang ◽  
Byoung Joon Kim ◽  
Soo Jin Park ◽  
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Alejandro César López-Echaury ◽  
José Antonio Saucedo-Ortiz ◽  
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Abstract Mesenchymal stem cells are a potential therapeutic candidate for cerebral infarction due to their anti-inflammatory proprieties. However, ensuring the engraftment of sufficient cells into the affected brain area remains a challenge. Herein, magnetic targeting techniques were used for the noninvasive transplantation of a large number of cells noninvasively. Mice subjected to permanent middle cerebral artery occlusion surgery were administered mesenchymal stem cells labeled or not with iron oxide@polydopamine nanoparticles by tail vein injection. Iron oxide@polydopamine particles were characterized by transmission electron microscopy, and labeled mesenchymal stem cells were characterized by flow cytometry and their differentiation potential was assessed in vitro . Following the systemic injection of iron oxide@polydopamine-labeled mesenchymal stem cells into permanent transient middle cerebral artery occlusion-induced mice, magnetic navigation increased the MSCs localization to the brain lesion site and reduced the lesion volume. Treatment with iron oxide@polydopamine-labeled mesenchymal stem cells also significantly inhibited M1 microglia polarization and increased M2 microglia cell infiltration. Furthermore, western blotting and immunohistochemical analysis demonstrated that microtubule-associated protein 2 and NeuN levels were upregulated the brain tissue of mice treated with iron oxide@polydopamine-labeled mesenchymal stem cells. Thus, iron oxide@polydopamine-labeled mesenchymal stem cells attenuated brain injury and protected neurons by preventing pro-inflammatory microglia activation. Overall, the proposed iron oxide@polydopamine-labeled mesenchymal stem cells approach may overcome the major drawback of the conventional MSCs therapy for the treatment of cerebral infarction.


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