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Investigating the Interactions of Glioma Stem Cells in the Perivascular Niche at Single-Cell Resolution using a Microfluidic Tumor Microenvironment Model.

Authors:
Emmanuela A Adjei-Sowah Samantha A O'Connor Jaimeson Veldhuizen Costanza Lo Cascio Christopher Plaisier Shwetal Mehta Mehdi Nikkhah

Adv Sci (Weinh) 2022 May 26:e2201436. Epub 2022 May 26.

School of Biological and Health Systems Engineering, Arizona State University, Tempe, AZ, 85287-9709, USA.

The perivascular niche (PVN) is a glioblastoma tumor microenvironment (TME) that serves as a safe haven for glioma stem cells (GSCs), and acts as a reservoir that inevitably leads to tumor recurrence. Understanding cellular interactions in the PVN that drive GSC treatment resistance and stemness is crucial to develop lasting therapies for glioblastoma. The limitations of in vivo models and in vitro assays have led to critical knowledge gaps regarding the influence of various cell types in the PVN on GSCs behavior. This study developed an organotypic triculture microfluidic model as a means to recapitulate the PVN and study its impact on GSCs. This triculture platform, comprised of endothelial cells (ECs), astrocytes, and GSCs, is used to investigate GSC invasion, proliferation and stemness. Both ECs and astrocytes significantly increased invasiveness of GSCs. This study futher identified 15 ligand-receptor pairs using single-cell RNAseq with putative chemotactic mechanisms of GSCs, where the receptor is up-regulated in GSCs and the diffusible ligand is expressed in either astrocytes or ECs. Notably, the ligand-receptor pair SAA1-FPR1 is demonstrated to be involved in chemotactic invasion of GSCs toward PVN. The novel triculture platform presented herein can be used for therapeutic development and discovery of molecular mechanisms driving GSC biology.

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http://dx.doi.org/10.1002/advs.202201436DOI Listing
May 2022

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Sen Liu Xu Chen Tianxin Lin

J Adv Res 2022 Jul 24;39:187-202. Epub 2021 Nov 24.

Department of Urology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China; Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China; Guangdong Provincial Clinical Research Center for Urological Diseases, China. Electronic address:

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Int Rev Cell Mol Biol 2022 30;369:45-70. Epub 2022 May 30.

Institute of Immunology and Infection Research, School of Biological Sciences, University of Edinburgh, Edinburgh, United Kingdom; Department of Immune Medicine, University Regensburg, Regensburg, Germany; Institute of Clinical Chemistry and Laboratory Medicine, University Hospital Regensburg, Regensburg, Germany; Institute of Pathology, University Regensburg, Regensburg, Germany. Electronic address:

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Int Rev Cell Mol Biol 2022 30;369:107-141. Epub 2022 May 30.

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J Chem Neuroanat 2022 Jun 28:102133. Epub 2022 Jun 28.

The Third Affiliated Hospital, Beijing University of Chinese Medicine, Beijing, China; Institute of acupuncture and moxibustion in cancer care, Beijing University of Chinese Medicine. Electronic address:

Purpose: The aim of this study was to investigate the anti-tumor effect of electroacupuncture (EA) on mice bearing breast tumors by regulating p75 neurotrophin receptor (p75NTR) and remodelling intratumoral innervation.

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Yanan Li Lingyun He Jiamin Chen Jinfeng Wang Shujing Zhao Xingxing Liu Xiaoling Guo Ying Wu Xian Shen Chao Li

Int J Biol Macromol 2022 Jun 28. Epub 2022 Jun 28.

The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, 109 Xueyuan West Road, Wenzhou 325027, PR China. Electronic address:

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June 2022
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