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微流控处理干细胞用于自体细胞替代。

Microfluidic processing of stem cells for autologous cell replacement.

机构信息

The George W. Woodruff School of Mechanical Engineering, Georgia Institute of Technology, Atlanta, Georgia, USA.

Institute for Vision Research, Department of Ophthalmology and Visual Science, Carver College of Medicine, University of Iowa, Iowa City, Iowa, USA.

出版信息

Stem Cells Transl Med. 2021 Oct;10(10):1384-1393. doi: 10.1002/sctm.21-0080. Epub 2021 Jun 22.

Abstract

Autologous photoreceptor cell replacement is one of the most promising approaches currently under development for the treatment of inherited retinal degenerative blindness. Unlike endogenous stem cell populations, induced pluripotent stem cells (iPSCs) can be differentiated into both rod and cone photoreceptors in high numbers, making them ideal for this application. That said, in addition to photoreceptor cells, state of the art retinal differentiation protocols give rise to all of the different cell types of the normal retina, the majority of which are not required and may in fact hinder successful photoreceptor cell replacement. As such, following differentiation photoreceptor cell enrichment will likely be required. In addition, to prevent the newly generated photoreceptor cells from suffering the same fate as the patient's original cells, correction of the patient's disease-causing genetic mutations will be necessary. In this review we discuss literature pertaining to the use of different cell sorting and transfection approaches with a focus on the development and use of novel next generation microfluidic devices. We will discuss how gold standard strategies have been used, the advantages and disadvantages of each, and how novel microfluidic platforms can be incorporated into the clinical manufacturing pipeline to reduce the complexity, cost, and regulatory burden associated with clinical grade production of photoreceptor cells for autologous cell replacement.

摘要

自体感光细胞替代疗法是目前正在开发的治疗遗传性视网膜退行性失明的最有前途的方法之一。与内源性干细胞群体不同,诱导多能干细胞(iPSC)可以大量分化为视杆细胞和视锥细胞,这使它们成为这种应用的理想选择。也就是说,除了感光细胞外,最先进的视网膜分化方案还会产生正常视网膜的所有不同细胞类型,其中大多数细胞类型不需要,实际上可能会阻碍成功的感光细胞替代。因此,在分化后可能需要进行感光细胞富集。此外,为了防止新生成的感光细胞遭受与患者原始细胞相同的命运,有必要纠正患者的致病基因突变。在这篇综述中,我们讨论了与使用不同细胞分选和转染方法相关的文献,重点是新型下一代微流控设备的开发和使用。我们将讨论金标准策略的使用情况,每种策略的优缺点,以及如何将新型微流控平台纳入临床制造管道,以降低与自体细胞替代的临床级感光细胞生产相关的复杂性、成本和监管负担。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bd62/8459636/0a6ffa1fdca7/SCT3-10-1384-g003.jpg

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