Investigating the Interactions of Glioma Stem Cells in the Perivascular Niche at Single‐Cell Resolution using a Microfluidic Tumor Microenvironment Model
Abstract 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 ste...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2022-07-01
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| Series: | Advanced Science |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/advs.202201436 |
| _version_ | 1818043617427587072 |
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| author | Emmanuela A. Adjei‐Sowah Samantha A. O'Connor Jaimeson Veldhuizen Costanza Lo Cascio Christopher Plaisier Shwetal Mehta Mehdi Nikkhah |
| author_facet | Emmanuela A. Adjei‐Sowah Samantha A. O'Connor Jaimeson Veldhuizen Costanza Lo Cascio Christopher Plaisier Shwetal Mehta Mehdi Nikkhah |
| author_sort | Emmanuela A. Adjei‐Sowah |
| collection | DOAJ |
| description | Abstract 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. |
| first_indexed | 2024-12-10T09:05:04Z |
| format | Article |
| id | doaj.art-2b3e5fa4d610453cbd18c3e6dc9e5779 |
| institution | Directory Open Access Journal |
| issn | 2198-3844 |
| language | English |
| last_indexed | 2024-12-10T09:05:04Z |
| publishDate | 2022-07-01 |
| publisher | Wiley |
| record_format | Article |
| series | Advanced Science |
| spelling | doaj.art-2b3e5fa4d610453cbd18c3e6dc9e57792022-12-22T01:55:10ZengWileyAdvanced Science2198-38442022-07-01921n/an/a10.1002/advs.202201436Investigating the Interactions of Glioma Stem Cells in the Perivascular Niche at Single‐Cell Resolution using a Microfluidic Tumor Microenvironment ModelEmmanuela A. Adjei‐Sowah0Samantha A. O'Connor1Jaimeson Veldhuizen2Costanza Lo Cascio3Christopher Plaisier4Shwetal Mehta5Mehdi Nikkhah6School of Biological and Health Systems Engineering Arizona State University Tempe AZ 85287‐9709 USASchool of Biological and Health Systems Engineering Arizona State University Tempe AZ 85287‐9709 USASchool of Biological and Health Systems Engineering Arizona State University Tempe AZ 85287‐9709 USAIvy Brain Tumor Center, Barrow Neurological Institute St. Joseph's Hospital and Medical Center 350 W Thomas Rd Phoenix AZ 85013 USASchool of Biological and Health Systems Engineering Arizona State University Tempe AZ 85287‐9709 USAIvy Brain Tumor Center, Barrow Neurological Institute St. Joseph's Hospital and Medical Center 350 W Thomas Rd Phoenix AZ 85013 USASchool of Biological and Health Systems Engineering Arizona State University Tempe AZ 85287‐9709 USAAbstract 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.https://doi.org/10.1002/advs.202201436glioblastomainvasionperivascular nichetranscriptomicstumor microenvironment |
| spellingShingle | Emmanuela A. Adjei‐Sowah Samantha A. O'Connor Jaimeson Veldhuizen Costanza Lo Cascio Christopher Plaisier Shwetal Mehta Mehdi Nikkhah Investigating the Interactions of Glioma Stem Cells in the Perivascular Niche at Single‐Cell Resolution using a Microfluidic Tumor Microenvironment Model Advanced Science glioblastoma invasion perivascular niche transcriptomics tumor microenvironment |
| title | Investigating the Interactions of Glioma Stem Cells in the Perivascular Niche at Single‐Cell Resolution using a Microfluidic Tumor Microenvironment Model |
| title_full | Investigating the Interactions of Glioma Stem Cells in the Perivascular Niche at Single‐Cell Resolution using a Microfluidic Tumor Microenvironment Model |
| title_fullStr | Investigating the Interactions of Glioma Stem Cells in the Perivascular Niche at Single‐Cell Resolution using a Microfluidic Tumor Microenvironment Model |
| title_full_unstemmed | Investigating the Interactions of Glioma Stem Cells in the Perivascular Niche at Single‐Cell Resolution using a Microfluidic Tumor Microenvironment Model |
| title_short | Investigating the Interactions of Glioma Stem Cells in the Perivascular Niche at Single‐Cell Resolution using a Microfluidic Tumor Microenvironment Model |
| title_sort | investigating the interactions of glioma stem cells in the perivascular niche at single cell resolution using a microfluidic tumor microenvironment model |
| topic | glioblastoma invasion perivascular niche transcriptomics tumor microenvironment |
| url | https://doi.org/10.1002/advs.202201436 |
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