Liu Xiao Yu Eileen, Park Eugene, Barretto Tanya, Liu Elaine, Ferrier Graham A, Tavakkoli Jahan, J Baker Andrew
Institute of Medical Science, University of Toronto, Toronto, Canada.
Keenan Research Centre, Li Ka Shing Knowledge Institute, St. Michael's Hospital, Toronto, Canada.
Zebrafish. 2020 May 20. doi: 10.1089/zeb.2020.1859.
The pathophysiological events of secondary brain injury contribute to poor outcome after traumatic brain injury (TBI). The neuroprotective effects of mesenchymal cells have been extensively studied and evidence suggests that their effects are mostly mediated through paracrine effects. Human umbilical cord perivascular cells (HUCPVCs) are mesenchymal stem cells with potential therapeutic value in TBI. In this study, we assessed the effect of HUCPVC-conditioned media (CM) in an established adult zebrafish model of TBI induced by pulsed high-intensity focused ultrasound (pHIFU). This model demonstrates similarities to mammalian outcome after TBI. Administration of HUCPVC-CM 1 h postinjury (hpi) resulted in improved outcome after pHIFU-induced TBI. Western blot and immunohistochemistry results demonstrated that the HUCPVC-CM reduced ( < 0.05) reactive astrogliosis at 24 hpi. Moreover, at 24 hpi, the HUCPVC-CM treatment resulted in reduced apoptosis in HUCPVC-CM-treated zebrafish. Behavioral analysis demonstrated improvement in locomotor activity ( < 0.05) and anxiety ( < 0.05) at 6 and 24 hpi following HUCPVC-CM treatment. Overall, HUCPVC-CM treatment improved acute outcome measures in pHIFU-injured zebrafish. Collectively, the data demonstrate a cell-free treatment approach for traumatic brain injuries.
继发性脑损伤的病理生理事件会导致创伤性脑损伤（TBI）后预后不良。间充质细胞的神经保护作用已得到广泛研究，证据表明其作用大多通过旁分泌效应介导。人脐带血管周围细胞（HUCPVCs）是间充质干细胞，在TBI中具有潜在治疗价值。在本研究中，我们评估了HUCPVC条件培养基（CM）对已建立的成年斑马鱼脉冲高强度聚焦超声（pHIFU）诱导的TBI模型的影响。该模型显示出与TBI后哺乳动物预后的相似性。损伤后1小时（hpi）给予HUCPVC-CM可改善pHIFU诱导的TBI后的预后。蛋白质印迹和免疫组织化学结果表明，HUCPVC-CM在24 hpi时可减少（<0.05）反应性星形胶质细胞增生。此外，在24 hpi时，HUCPVC-CM处理可减少HUCPVC-CM处理的斑马鱼的细胞凋亡。行为分析表明，HUCPVC-CM处理后6小时和24小时，运动活性（<0.05）和焦虑（<0.05）有所改善。总体而言，HUCPVC-CM处理改善了pHIFU损伤斑马鱼的急性预后指标。总之，这些数据证明了一种用于创伤性脑损伤的无细胞治疗方法。
