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基于诱导多能干细胞的 2019 冠状病毒病疾病建模和前瞻性免疫治疗。

Induced pluripotent stem cell-based disease modeling and prospective immune therapy for coronavirus disease 2019.

机构信息

GROW Research Laboratory, Narayana Nethralaya Foundation, Bangalore, India.

Cornea and Refractive Surgery, Narayana Nethralaya, Bangalore, India.

出版信息

Cytotherapy. 2022 Mar;24(3):235-248. doi: 10.1016/j.jcyt.2021.08.003. Epub 2021 Sep 14.

Abstract

The emergence of the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic poses a never before seen challenge to human health and the economy. Considering its clinical impact, with no streamlined therapeutic strategies in sight, it is crucial to understand the infection process of SARS-CoV-2. Our limited knowledge of the mechanisms underlying SARS-CoV-2 infection impedes the development of alternative therapeutics to address the pandemic. This aspect can be addressed by modeling SARS-CoV-2 infection in the human context to facilitate drug screening and discovery. Human induced pluripotent stem cell (iPSC)-derived lung epithelial cells and organoids recapitulating the features and functionality of the alveolar cell types can serve as an in vitro human model and screening platform for SARS-CoV-2. Recent studies suggest an immune system asynchrony leading to compromised function and a decreased proportion of specific immune cell types in coronavirus disease 2019 (COVID-19) patients. Replenishing these specific immune cells may serve as useful treatment modality against SARS-CoV-2 infection. Here the authors review protocols for deriving lung epithelial cells, alveolar organoids and specific immune cell types, such as T lymphocytes and natural killer cells, from iPSCs with the aim to aid investigators in making relevant in vitro models of SARS-CoV-2 along with the possibility derive immune cell types to treat COVID-19.

摘要

新型严重急性呼吸综合征冠状病毒 2(SARS-CoV-2)大流行的出现对人类健康和经济构成了前所未有的挑战。考虑到其临床影响,由于没有可行的治疗策略,了解 SARS-CoV-2 的感染过程至关重要。我们对 SARS-CoV-2 感染机制的了解有限,这阻碍了针对这一大流行病的替代疗法的发展。可以通过在人类环境中模拟 SARS-CoV-2 感染来解决这一方面的问题,从而促进药物筛选和发现。人类诱导多能干细胞(iPSC)衍生的肺上皮细胞和类器官可以重现肺泡细胞类型的特征和功能,可作为体外人类模型和 SARS-CoV-2 的筛选平台。最近的研究表明,免疫系统存在不同步现象,导致 2019 年冠状病毒病(COVID-19)患者的功能受损和特定免疫细胞类型的比例降低。补充这些特定的免疫细胞可能是对抗 SARS-CoV-2 感染的有用治疗方法。作者在此回顾了从 iPSC 中衍生肺上皮细胞、肺泡类器官和特定免疫细胞类型(如 T 淋巴细胞和自然杀伤细胞)的方案,旨在帮助研究人员建立 SARS-CoV-2 的相关体外模型,并有可能衍生免疫细胞类型来治疗 COVID-19。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7d09/8437760/c332e362afa3/ga1_lrg.jpg

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