Mandeep K Marway, Dickyi Bhagentsang, Chitra Venugopal, Sheila K Singh, Ryan G Wylie, Boyang Zhang
{"title":"跨越屏障：研究单核细胞跨越内皮屏障迁移的体外癌症模型。","authors":"Mandeep K Marway, Dickyi Bhagentsang, Chitra Venugopal, Sheila K Singh, Ryan G Wylie, Boyang Zhang","doi":"10.1021/acsbiomaterials.5c00783","DOIUrl":null,"url":null,"abstract":"<p><p>Monocytes originate in the bone marrow and make up 2-10% of all white blood cells, circulating in the blood to damaged tissue and disease sites, where they differentiate into macrophages or dendritic cells. In solid tumors such as glioblastoma, monocytes recruited from the blood to the tumor site differentiate into tumor-associated macrophages (TAMs), which play a key role in tumor progression and metastasis. The endothelial vessel wall plays a significant role in the migration, activation, and polarization of these monocytes. Therefore, it is crucial to incorporate an endothelial cell (EC) barrier within an <i>in vitro</i> cancer model for elucidating transendothelial migration of monocytes along with high-throughput screening capabilities. The IFlowPlate is a high-throughput organ-on-a-chip device created on a 384-well plate modified by creating 128 tissue compartments created by connecting three wells with a single channel to model interstitial flow. Due to its simple design, it can be easily modified to model any tissue type. To study the effects of the EC barrier on tumor-promoted monocyte migration, cancer spheroids were embedded within a fibrin hydrogel with an EC barrier on the hydrogel surface to mimic the vessel wall. THP-1 monocyte migration was observed in the presence of patient-derived glioblastoma cancer spheroids and interstitial flow, and the presence of the human umbilical vein endothelial cell (HUVEC) barrier slowed and reduced monocyte migration compared with controls without EC barriers. Inflammatory cytokines, such as granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin-6 (IL-6), interleukin-10 (IL-10), and interleukin-1β (IL-1β) secretion levels increased, while tumor necrosis factor α (TNF-α) and interleukin-12p40 (IL-12p40) levels decreased and monocyte chemoattractant protein-1 (MCP-1) and interleukin-8 (IL-8) levels remained unchanged in the presence of the EC barrier and spheroids, confirming the importance of the EC barrier for monocyte activation and migration. The EC barrier plays a crucial role in promoting and controlling monocyte migration <i>in vivo</i>. The IFlowPlate with a functional EC barrier can be used to model monocyte migration <i>in vitro</i> to study the role of monocytes in cancer prognosis.</p>","PeriodicalId":8,"journal":{"name":"ACS Biomaterials Science & Engineering","volume":" ","pages":""},"PeriodicalIF":5.4000,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Crossing Barriers<i>: In Vitro</i> Cancer Model for Studying Monocyte Migration across Endothelial Barriers.\",\"authors\":\"Mandeep K Marway, Dickyi Bhagentsang, Chitra Venugopal, Sheila K Singh, Ryan G Wylie, Boyang Zhang\",\"doi\":\"10.1021/acsbiomaterials.5c00783\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Monocytes originate in the bone marrow and make up 2-10% of all white blood cells, circulating in the blood to damaged tissue and disease sites, where they differentiate into macrophages or dendritic cells. In solid tumors such as glioblastoma, monocytes recruited from the blood to the tumor site differentiate into tumor-associated macrophages (TAMs), which play a key role in tumor progression and metastasis. The endothelial vessel wall plays a significant role in the migration, activation, and polarization of these monocytes. Therefore, it is crucial to incorporate an endothelial cell (EC) barrier within an <i>in vitro</i> cancer model for elucidating transendothelial migration of monocytes along with high-throughput screening capabilities. The IFlowPlate is a high-throughput organ-on-a-chip device created on a 384-well plate modified by creating 128 tissue compartments created by connecting three wells with a single channel to model interstitial flow. Due to its simple design, it can be easily modified to model any tissue type. To study the effects of the EC barrier on tumor-promoted monocyte migration, cancer spheroids were embedded within a fibrin hydrogel with an EC barrier on the hydrogel surface to mimic the vessel wall. THP-1 monocyte migration was observed in the presence of patient-derived glioblastoma cancer spheroids and interstitial flow, and the presence of the human umbilical vein endothelial cell (HUVEC) barrier slowed and reduced monocyte migration compared with controls without EC barriers. Inflammatory cytokines, such as granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin-6 (IL-6), interleukin-10 (IL-10), and interleukin-1β (IL-1β) secretion levels increased, while tumor necrosis factor α (TNF-α) and interleukin-12p40 (IL-12p40) levels decreased and monocyte chemoattractant protein-1 (MCP-1) and interleukin-8 (IL-8) levels remained unchanged in the presence of the EC barrier and spheroids, confirming the importance of the EC barrier for monocyte activation and migration. The EC barrier plays a crucial role in promoting and controlling monocyte migration <i>in vivo</i>. 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Crossing Barriers: In Vitro Cancer Model for Studying Monocyte Migration across Endothelial Barriers.
Monocytes originate in the bone marrow and make up 2-10% of all white blood cells, circulating in the blood to damaged tissue and disease sites, where they differentiate into macrophages or dendritic cells. In solid tumors such as glioblastoma, monocytes recruited from the blood to the tumor site differentiate into tumor-associated macrophages (TAMs), which play a key role in tumor progression and metastasis. The endothelial vessel wall plays a significant role in the migration, activation, and polarization of these monocytes. Therefore, it is crucial to incorporate an endothelial cell (EC) barrier within an in vitro cancer model for elucidating transendothelial migration of monocytes along with high-throughput screening capabilities. The IFlowPlate is a high-throughput organ-on-a-chip device created on a 384-well plate modified by creating 128 tissue compartments created by connecting three wells with a single channel to model interstitial flow. Due to its simple design, it can be easily modified to model any tissue type. To study the effects of the EC barrier on tumor-promoted monocyte migration, cancer spheroids were embedded within a fibrin hydrogel with an EC barrier on the hydrogel surface to mimic the vessel wall. THP-1 monocyte migration was observed in the presence of patient-derived glioblastoma cancer spheroids and interstitial flow, and the presence of the human umbilical vein endothelial cell (HUVEC) barrier slowed and reduced monocyte migration compared with controls without EC barriers. Inflammatory cytokines, such as granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin-6 (IL-6), interleukin-10 (IL-10), and interleukin-1β (IL-1β) secretion levels increased, while tumor necrosis factor α (TNF-α) and interleukin-12p40 (IL-12p40) levels decreased and monocyte chemoattractant protein-1 (MCP-1) and interleukin-8 (IL-8) levels remained unchanged in the presence of the EC barrier and spheroids, confirming the importance of the EC barrier for monocyte activation and migration. The EC barrier plays a crucial role in promoting and controlling monocyte migration in vivo. The IFlowPlate with a functional EC barrier can be used to model monocyte migration in vitro to study the role of monocytes in cancer prognosis.
期刊介绍：
ACS Biomaterials Science & Engineering is the leading journal in the field of biomaterials, serving as an international forum for publishing cutting-edge research and innovative ideas on a broad range of topics:
Applications and Health – implantable tissues and devices, prosthesis, health risks, toxicology
Bio-interactions and Bio-compatibility – material-biology interactions, chemical/morphological/structural communication, mechanobiology, signaling and biological responses, immuno-engineering, calcification, coatings, corrosion and degradation of biomaterials and devices, biophysical regulation of cell functions
Characterization, Synthesis, and Modification – new biomaterials, bioinspired and biomimetic approaches to biomaterials, exploiting structural hierarchy and architectural control, combinatorial strategies for biomaterials discovery, genetic biomaterials design, synthetic biology, new composite systems, bionics, polymer synthesis
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Modeling and Informatics Tools – scaling methods to guide biomaterial design, predictive algorithms for structure-function, biomechanics, integrating bioinformatics with biomaterials discovery, metabolomics in the context of biomaterials
Tissue Engineering and Regenerative Medicine – basic and applied studies, cell therapies, scaffolds, vascularization, bioartificial organs, transplantation and functionality, cellular agriculture
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