小柯机器人

美国耶鲁大学Nenad Sestan研究小组实现长时间全身温热缺血后的细胞恢复。相关论文于2022年8月3日在线发表在《自然》杂志上。

研究人员报道了OrganEx，这是BrainEx体外脉冲灌注系统和细胞保护灌注液的改编，用于猪的全身设置。在温热缺血1小时后，OrganEx的应用保持了组织的完整性，减少了细胞死亡，并恢复了多个重要器官的选定分子和细胞过程。相应地，单核转录组分析显示了器官和细胞类型的特定基因表达模式，反映了特定的分子和细胞修复过程。这些分析包括了在确定的缺血时间间隔和跨越多个器官的灌注干预期间细胞类型特异性变化的全面资源，它揭示了大型哺乳动物在长期全身温热缺血后细胞恢复的潜力未得到充分重视。

据悉，在血流停止或类似的缺血暴露后，哺乳动物细胞中开始出现有害的分子级联，最终导致其死亡。然而，通过有针对性的干预，这些过程可以被缓解或逆转，甚至在死后数分钟或数小时内，正如使用BrainEx技术在分离的猪脑中所报告的那样。迄今为止，将单器官干预转化为完整的全身应用仍然受到循环系统和多系统生理学挑战的阻碍。

附：英文原文

Title: Cellular recovery after prolonged warm ischaemia of the whole body

Author: Andrijevic, David, Vrselja, Zvonimir, Lysyy, Taras, Zhang, Shupei, Skarica, Mario, Spajic, Ana, Dellal, David, Thorn, Stephanie L., Duckrow, Robert B., Ma, Shaojie, Duy, Phan Q., Isiktas, Atagun U., Liang, Dan, Li, Mingfeng, Kim, Suel-Kee, Daniele, Stefano G., Banu, Khadija, Perincheri, Sudhir, Menon, Madhav C., Huttner, Anita, Sheth, Kevin N., Gobeske, Kevin T., Tietjen, Gregory T., Zaveri, Hitten P., Latham, Stephen R., Sinusas, Albert J., Sestan, Nenad

Issue&Volume: 2022-08-03

Abstract: After cessation of blood flow or similar ischaemic exposures, deleterious molecular cascades commence in mammalian cells, eventually leading to their death1,2. Yet with targeted interventions, these processes can be mitigated or reversed, even minutes or hours post mortem, as also reported in the isolated porcine brain using BrainEx technology3. To date, translating single-organ interventions to intact, whole-body applications remains hampered by circulatory and multisystem physiological challenges. Here we describe OrganEx, an adaptation of the BrainEx extracorporeal pulsatile-perfusion system and cytoprotective perfusate for porcine whole-body settings. After 1h of warm ischaemia, OrganEx application preserved tissue integrity, decreased cell death and restored selected molecular and cellular processes across multiple vital organs. Commensurately, single-nucleus transcriptomic analysis revealed organ- and cell-type-specific gene expression patterns that are reflective of specific molecular and cellular repair processes. Our analysis comprises a comprehensive resource of cell-type-specific changes during defined ischaemic intervals and perfusion interventions spanning multiple organs, and it reveals an underappreciated potential for cellular recovery after prolonged whole-body warm ischaemia in a large mammal.

DOI: 10.1038/s41586-022-05016-1

Source: https://www.nature.com/articles/s41586-022-05016-1

Nature：《自然》，创刊于1869年。隶属于施普林格·自然出版集团，最新IF：69.504
官方网址：http://www.nature.com/
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