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通过多穗柯因和曲古抑菌素A的混合物将人成纤维细胞完全小分子转化为神经外胚层细胞。

Full small molecule conversion of human fibroblasts to neuroectodermal cells via a cocktail of Dorsomorphin and Trichostatin A.

作者信息

Hosseini Farahabadi Samaneh Sadat, Ghaedi Kamran, Shoaraye-Nejati Alireza, Nasr-Esfahani Mohammad-Hossein

机构信息

Department of Cell and Molecular Biology and Microbiology, Faculty of Biological Science and Technology, University of Isfahan, Isfahan, Iran.

Department of Cellular Biotechnology at Cell Science Research Center, Royan Institute for Biotechnology, ACECR, Isfahan, Iran.

出版信息

Regen Ther. 2020 Jun 15;15:44-52. doi: 10.1016/j.reth.2020.05.003. eCollection 2020 Dec.

Abstract

A revolutionary new approach to produce efficient cells is to induce transdifferentiation to make it conventional in therapeutic strategies. In this paper, we describe a brief cocktail of small molecules including Dorsomorphin (DSM) and Trichostatin A (TSA) to produce safe neuroectodermal cells as a resource to produce various types of nervous system cells for a safe cytotherapy. Furthermore, in order to optimize this strategy, we implemented a cocktail of neurotrophic factors to enhance the viability of the cell. This modification was accompanied by pretreatment of the culture dishes with a combination of poly-l-ornithine and laminin and fibronectin. In order to decrease the length of protocol and transdifferentiation variation concomitantly, TSA was utilized as an epigenetic modulator. Finally, this improved protocol mediated neuroectodermal conversion of human fibroblasts within 12 days with an average efficiency of 24%, promising a fast strategy to produce neuroectodermal cells applicable for therapeutic purposes in neural damages. Here we induce neural cells by a cocktail consists of two small molecules of DSM and TSA. Our protocol is a 12 day protocol with the efficiency of 24% which is a more efficient one in comparison to previous protocols inducing neural cells. Consequently, our protocol shortens the path of in vitro and preclinical studies in the field of neural conversion and neuroregeneration.

摘要

一种生产高效细胞的全新方法是诱导转分化,使其在治疗策略中成为常规方法。在本文中,我们描述了一种包含多穗米诺(DSM)和曲古抑菌素A(TSA)的小分子组合,用于生产安全的神经外胚层细胞,作为生产用于安全细胞治疗的各种类型神经系统细胞的资源。此外,为了优化该策略,我们使用了一种神经营养因子组合来提高细胞的活力。这种改进伴随着用聚-L-鸟氨酸与层粘连蛋白和纤连蛋白的组合对培养皿进行预处理。为了同时缩短方案的时长并减少转分化的差异,TSA被用作一种表观遗传调节剂。最后,这种改进后的方案在12天内介导了人成纤维细胞向神经外胚层的转化,平均效率为24%,有望成为一种快速生产适用于神经损伤治疗目的神经外胚层细胞的策略。在这里,我们通过由DSM和TSA两种小分子组成的组合诱导神经细胞。我们的方案是一个为期12天的方案,效率为24%,与之前诱导神经细胞的方案相比,这是一个更有效的方案。因此,我们的方案缩短了神经转化和神经再生领域的体外和临床前研究路径。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cc72/7770348/16e9d7162f4b/gr1.jpg

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