A Novel Approach to Increase Glial Cell Populations in Brain Microphysiological Systems

Author:

Morales Pantoja Itzy E.1ORCID,Ding Lixuan1,Leite Paulo E. C.2ORCID,Marques Suelen A.3ORCID,Romero July Carolina1ORCID,Alam El Din Dowlette‐Mary1ORCID,Zack Donald J.4,Chamling Xitiz4ORCID,Smirnova Lena1ORCID

Affiliation:

1. Center for Alternatives to Animal Testing (CAAT) Department of Environmental Health and Engineering Bloomberg School of Public Health Johns Hopkins University Baltimore MD 21205 USA

2. Clinical Research Unit of the Antonio Pedro Hospital Fluminense Federal University Niteroi 24033‐900 Brazil

3. Laboratory of Neural Regeneration and Function Neurobiology Department Biology Institute Fluminense Federal University Niteroi 24210‐201 Brazil

4. Department of Ophthalmology Wilmer Eye Institute Johns Hopkins University School of Medicine Baltimore MD 21287 USA

Abstract

AbstractBrain microphysiological systems (bMPS) recapitulate human brain cellular architecture and functionality more closely than traditional monolayer cultures and have become increasingly relevant for the study of neurological function in health and disease. Existing 3D brain models vary in reflecting the relative populations of different cell types present in the human brain. Most models consist mainly of neurons, while glial cells represent a smaller portion of the cell populations. Here, by means of a chemically defined glial‐enriched medium (GEM), an improved method to expand the population of astrocytes and oligodendrocytes without compromising neuronal differentiation in bMPS, is presented. An important finding is that astrocytes also change in morphology when cultured in GEM, more closely recapitulating primary culture astrocytes. GEM bMPS are electro‐chemically active and show different patterns of calcium staining and flux. Synaptic vesicles and terminals observed by electron microscopy are also present. No significant changes in neuronal differentiation are observed by gene expression, however, GEM enhanced neurite outgrowth and cell migration, and differentially modulated neuronal maturation in two different cell lines. These results have the potential to significantly improve functionality of bMPS for the study of neurological diseases and drug discovery, contributing to the unmet need for safe human models.

Publisher

Wiley

Subject

General Medicine

Reference59 articles.

1. Engineering of human brain organoids with a functional vascular-like system

2. Developing human pluripotent stem cell-based cerebral organoids with a controllable microglia ratio for modeling brain development and pathology

3. J. F.Quintana P.Chandrasegaran M. C.Sinton E. M.Briggs T. D.Otto R.Heslop Single cell and spatial transcriptomic analyses reveal microglia‐plasma cell crosstalk in the brain during Trypanosoma brucei infection.

Cited by 4 articles. 订阅此论文施引文献 订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3