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Full small molecule conversion of human fibroblasts to neuroectodermal cells via a cocktail of Dorsomorphin and Trichostatin A
Regenerative Therapy ( IF 3.4 ) Pub Date : 2020-06-15 , DOI: 10.1016/j.reth.2020.05.003
Samaneh Sadat Hosseini Farahabadi , Kamran Ghaedi , Alireza Shoaraye-nejati , Mohammad-Hossein Nasr-Esfahani

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.



中文翻译:

通过Dorsomorphin和Trichostatin 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

一种产生有效细胞的革命性新方法是诱导转分化,使其在治疗策略中变得常规。在本文中,我们描述了简短的小分子混合物,其中包括Dorsomorphin(DSM)和Trichostatin A(TSA)来生产安全的神经外胚层细胞,作为生产各种类型的神经系统细胞进行安全细胞疗法的资源。此外,为了优化此策略,我们实施了一系列神经营养因子来增强细胞活力。该变形例是伴随着的培养皿预处理聚的组合-鸟氨酸和层粘连蛋白和纤连蛋白。为了同时减少方案的长度和转分化差异,TSA被用作表观遗传调节剂。最后,这种改进的方案在12天内以平均24%的效率介导了人类成纤维细胞的神经外胚层转化,这有望产生一种可用于治疗神经损伤的神经外胚层细胞的快速策略。在这里,我们通过由两个小分子DSM和TSA组成的混合物诱导神经细胞。我们的协议是12天协议,效率为24%,与以前的诱导神经细胞协议相比,效率更高。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的路径。

更新日期:2020-06-15
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