新研究：干细胞有望治愈猴痘

$南京新百(SH600682)$  干细胞有望治愈猴痘！研究人员报道利用人诱导多能干细胞（iPSC）衍生皮肤类器官可用于探索猴痘病毒的感染和治疗药物筛选。相关研究结果发表在 Nature Microbiology 上。

人诱导多能干细胞具有的分化潜能允许其构建多种类器官，研究人员利用iPSC构建皮肤类器官重现人体皮肤的关键物理和生理特征，并且具有包括毛囊和皮脂腺在内的多种皮肤附件。采用气-液界面（ALI）培养系统，进一步促使皮肤类器官成熟接近于人类皮肤生理。基于构建的皮肤类器官，研究人员研究了MPXV在皮肤中的发病机制并测试了抗病毒药物。结果发现，该皮肤类器官支持猴痘病毒的有效感染，感染导致大量猴痘病毒转录本的表达，并影响宿主转录组。并且天花治疗药物Tecovirimat能够抑制感染性猴痘病毒颗粒的产生，显示该皮肤类器官模型系统在研究病毒-宿主相互作用和测试抗病毒药物方面的潜力。综上，该研究为研究MPXV在皮肤发病机制和抗病毒药物筛选开发了一种有效的iPSC衍生皮肤类器官模型。

推荐阅读原文：

Mpox virus infection and drug treatment modelled in human skin organoids.

Mpox virus (MPXV) primarily infects human skin to cause lesions. Currently, robust models that recapitulate skin infection by MPXV are lacking. Here we demonstrate that human induced pluripotent stem cell-derived skin organoids are susceptible to MPXV infection and support infectious virus production. Keratinocytes, the predominant cell type of the skin epithelium, effectively support MPXV infection. Using transmission electron microscopy, we visualized the four stages of intracellular virus particle assembly: crescent formation, immature virions, mature virions and wrapped virions. Transcriptional analysis showed that MPXV infection rewires the host transcriptome and triggers abundant expression of viral transcripts. Early treatment with the antiviral drug tecovirimat effectively inhibits infectious virus production and prevents host transcriptome rewiring. Delayed treatment with tecovirimat also inhibits infectious MPXV particle production, albeit to a lesser extent. This study establishes human skin organoids as a robust experimental model for studying MPXV infection, mapping virus-host interactions and testing therapeutics.