Topical tissue nano-transfection mediates non-viral stroma reprogramming and rescue.
Topical tissue nano-transfection mediates non-viral stroma reprogramming and rescue.
复制标题
DOI：
10.1038/nnano.2017.134
复制
发表时间：
2017-10
影响因子：
38.3
通讯作者：
Sen CK
中科院分区：
文献类型：
--
作者：
Gallego-Perez D;Pal D;Ghatak S;Malkoc V;Higuita-Castro N;Gnyawali S;Chang L;Liao WC;Shi J;Sinha M;Singh K;Steen E;Sunyecz A;Stewart R;Moore J;Ziebro T;Northcutt RG;Homsy M;Bertani P;Lu W;Roy S;Khanna S;Rink C;Sundaresan VB;Otero JJ;Lee LJ;Sen CK
尽管细胞疗法对于许多疾病来说是一种很有希望的策略，但目前的方法面临着主要的翻译障碍，包括有限的细胞来源和需要繁琐的前处理步骤(例如，分离、诱导多能性)。体内细胞重新编程有可能通过使用现成的细胞来源(例如成纤维细胞)并绕过体外前处理的需要，实现更有效的基于细胞的治疗。然而，现有的重新编程方法充满了警告，包括严重依赖病毒转染法。此外，衣壳大小的限制和/或现状方法(病毒和非病毒)的随机性带来了额外的限制，从而突出了需要更安全和更确定的体内重新编程方法。在这里，我们报告了一种新的但易于实现的非病毒方法，通过一个纳米通道装置对组织进行局部重新编程，分别用成熟的和新开发的诱导神经元和内皮重新编程模型进行了验证。我们通过使用两种损伤诱导的小鼠缺血模型拯救坏死性组织和整个肢体，证明了这种方法的简单性和实用性。
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.
登录
查看更多内容
通过确定的因素将成纤维细胞直接转化为功能性神经元。
影响因子：
64.8
作者：
Vierbuchen, Thomas;Ostermeier, Austin;Pang, Zhiping P.;Kokubu, Yuko;Suedhof, Thomas C.;Wernig, Marius
通讯作者：
Wernig, Marius
影响因子：
46.9
作者：
Cunningham, Justine J.;Ulbright, Thomas M.;Looijenga, Leendert H. J.
通讯作者：
Looijenga, Leendert H. J.
影响因子：
6.3
作者：
Khanna, Savita;Rink, Cameron;Sen, Chandan K.
通讯作者：
Sen, Chandan K.
影响因子：
5.2
作者：
Rosova, Ivana;Dao, Mo;Nolta, Jan A.
通讯作者：
Nolta, Jan A.
影响因子：
16.6
作者：
Grande, Andrew;Sumiyoshi, Kyoko;Lopez-Juarez, Alejandro;Howard, Jennifer;Sakthivel, Bhuvaneswari;Aronow, Bruce;Campbell, Kenneth;Nakafuku, Masato
通讯作者：
Nakafuku, Masato