Although cellular therapies represent a promising strategy for a number of conditions, current approaches face major translational hurdles, including limited cell sources and the need for cumbersome pre-processing steps (for example, isolation, induced pluripotency). In vivo cell reprogramming has the potential to enable more-effective cell-based therapies by using readily available cell sources (for example, fibroblasts) and circumventing the need for ex vivo pre-processing. Existing reprogramming methodologies, however, are fraught with caveats, including a heavy reliance on viral transfection. Moreover, capsid size constraints and/or the stochastic nature of status quo approaches (viral and non-viral) pose additional limitations, thus highlighting the need for safer and more deterministic in vivo reprogramming methods. Here, we report a novel yet simple-to-implement non-viral approach to topically reprogram tissues through a nanochannelled device validated with well-established and newly developed reprogramming models of induced neurons and endothelium, respectively. We demonstrate the simplicity and utility of this approach by rescuing necrotizing tissues and whole limbs using two murine models of injury-induced ischaemia.

中文翻译：

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局部组织纳米转染介导非病毒基质重编程和抢救。

尽管细胞疗法在许多情况下代表了一种有前途的策略，但是当前的方法面临着主要的翻译障碍，包括有限的细胞来源以及繁琐的预处理步骤（例如，分离，诱导多能性）。体内细胞重编程有潜力通过使用容易获得的细胞来源（例如成纤维细胞）并避免离体前处理的需要，实现更有效的基于细胞的疗法。但是，现有的重编程方法充满了警告，包括严重依赖病毒转染。此外，衣壳大小的限制和/或现状方法（病毒和非病毒）的随机性质带来了其他限制，因此强调了对更安全，更具确定性的体内重编程方法的需求。这里，我们报告了一种新颖但简单易行的非病毒方法，通过纳米通道的设备局部重编程组织，该设备分别用成熟的和新开发的诱导神经元和内皮重编程模型进行了验证。我们通过使用两种鼠伤性局部缺血模型来抢救坏死的组织和整个肢体，证明了这种方法的简单性和实用性。