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The therapeutic value of adipose-derived pericyte transplantation after intracerebral hemorrhage in rats

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Abstract

Intracerebral hemorrhage (ICH) is a devastating cerebrovascular associated with inflammation and BBB disruption. Pericytes plays a critical role in neurological diseases, while whether pericytes could be utilized to treat ICH remains to be elucidated. Here, we isolated CD146+CD34 pericytes from rat adipose tissues (ADPs). Fluorescence-activated cells maintained their cell morphology and differentiation potential and expressed pericytes markers (CD146, NG2, and PDGFRβ) but not endothelial markers (CD31, CD34, and CD45). ADPs transplantation improved the neuro-behavioral functions in ICH rats and resulted in decreased hematoma volume and neuron loss after ICH. Besides, ADPs graft restrained the infiltration of neutrophils and reactive microgliosis after ICH injury around the peri-hematoma area of rats, as evidenced by increased Iba1- and MPO immunoreactivity. The transplanted pericytes were covered on endothelial cells, and promoted angiogenesis and vascular basement membrane formation in the peri-hematoma area of ICH rats, as shown by double staining of PDGFRβ and CD31/CollagenIV. The decreased brain water content and Evans Blue leakage proved the protective role of ADPs graft on BBB permeability. Finally, transplanted ADPs increased the expression of VE-cadherin, ZO-1, and claudin-5, leading to stable endothelial cell-cell adhesion and tight junction. In conclusion, the transplantation of APDs improved neuronal after ICH, which involved different mechanisms including neuroinflammation regulation and BBB dysfunction recovery. Our results supported that ADPs might be the ideal cell type for ICH therapy and provided insights into the potential cell therapy for further ICH treatment.

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Data Availability

The data supporting the findings of this study are available from the corresponding author upon reasonable requests.

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Funding

This work was supported by the Liuzhou Science and Technology Development Project [grant numbers 2021CBB0105].

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Authors

Contributions

Xin Zhang: Conceptualization, Methodology, Writing - Original Draft; Ying Zhou: Conceptualization, Methodology, Visualization; Qiongxia Liu: Data Curation, Visualization; Fang Wang: Resources, Data Curation; Lin Fu: Validation; Yizhi Wei: Data Curation; Yuanliang Ye: Data Curation; Yujie Guo: Conceptualization, Writing - Review & Editing, Funding acquisition.

Corresponding author

Correspondence to Yujie Guo.

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All animal protocols were approved by Committee for the Use and Care of Experimental Animals of Guangxi Medical University.

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The authors have no relevant financial or non-financial interests to disclose.

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Zhang, X., Zhou, Y., Liu, Q. et al. The therapeutic value of adipose-derived pericyte transplantation after intracerebral hemorrhage in rats. J Mol Histol 54, 499–508 (2023). https://doi.org/10.1007/s10735-023-10140-x

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  • DOI: https://doi.org/10.1007/s10735-023-10140-x

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