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双向穿梭:外周血单个核细胞的附加型载体重编程为诱导多能干细胞,以及随后分化为心肌细胞和神经元-星形胶质细胞共培养物。

Going Back and Forth: Episomal Vector Reprogramming of Peripheral Blood Mononuclear Cells to Induced Pluripotent Stem Cells and Subsequent Differentiation into Cardiomyocytes and Neuron-Astrocyte Co-cultures.

机构信息

Centre for Health Protection, National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands.

Institute for Risk Assessment Sciences (IRAS), Utrecht University, Utrecht, The Netherlands.

出版信息

Cell Reprogram. 2020 Dec;22(6):300-310. doi: 10.1089/cell.2020.0040. Epub 2020 Nov 3.

DOI:10.1089/cell.2020.0040
PMID:33146557
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7757589/
Abstract

Human induced pluripotent stem cells (iPSCs) can capture the diversity in the general human population as well as provide deeper insight in cellular mechanisms. This makes them suitable to study both fundamental and applied research subjects, such as disease modeling, gene-environment interactions, personalized medicine, and chemical toxicity. In an independent laboratory, we were able to generate iPSCs originating from human peripheral blood mononuclear cells according to a modified version of a temporal episomal vector (EV)-based induction method. The iPSCs could subsequently be differentiated into two different lineages: mesoderm-derived cardiomyocytes and ectoderm-derived neuron-astrocyte co-cultures. It was shown that the neuron-astrocyte culture developed a mature phenotype within the course of five weeks and depending on the medium composition, network formation and neuron-astrocyte cell ratios could be modified. Although previously it has been described that iPSCs generated with this EV-based induction protocol could differentiate to mesenchymal stem cells, hepatocytes, cardiomyocytes, and basic neuronal cultures, we now demonstrate differentiation into a culture containing both neurons and astrocytes.

摘要

人类诱导多能干细胞 (iPSCs) 可以捕捉一般人群的多样性,并提供对细胞机制的更深入了解。这使它们适合研究基础和应用研究课题,如疾病建模、基因-环境相互作用、个性化医疗和化学毒性。在一个独立的实验室中,我们能够根据一种经过改良的基于瞬时表达载体 (EV) 的诱导方法,从人外周血单核细胞中生成 iPSCs。随后,这些 iPSCs 可以分化为两种不同的谱系:中胚层来源的心肌细胞和外胚层来源的神经元-星形胶质细胞共培养物。结果表明,神经元-星形胶质细胞培养在五周的时间内发展出成熟的表型,并且可以根据培养基组成来修改网络形成和神经元-星形胶质细胞的比例。尽管以前已经描述过使用这种基于 EV 的诱导方案生成的 iPSCs 可以分化为间充质干细胞、肝细胞、心肌细胞和基本神经元培养物,但我们现在证明了可以分化为包含神经元和星形胶质细胞的培养物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5e8/7757589/a11148bd883d/cell.2020.0040_figure5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5e8/7757589/61fb6c24842d/cell.2020.0040_figure1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5e8/7757589/b40d46d0b889/cell.2020.0040_figure2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5e8/7757589/38dcd1209cb0/cell.2020.0040_figure3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5e8/7757589/40ab8b8d416f/cell.2020.0040_figure4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5e8/7757589/a11148bd883d/cell.2020.0040_figure5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5e8/7757589/61fb6c24842d/cell.2020.0040_figure1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5e8/7757589/b40d46d0b889/cell.2020.0040_figure2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5e8/7757589/38dcd1209cb0/cell.2020.0040_figure3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5e8/7757589/40ab8b8d416f/cell.2020.0040_figure4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5e8/7757589/a11148bd883d/cell.2020.0040_figure5.jpg

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