Pericytes and shear stress each alter the shape of a self-assembled vascular network

Fujimoto, Kazuya; Erickson, Scott; Nakayama, Masamune; Ihara, Hroki; Sugihara, Kei; Nashimoto, Yuji; Nishiyama, Koichi; Miura, Takashi; Yokokawa, Ryuji

doi:10.1039/d2lc00605g

Cited by 11 publications

(7 citation statements)

References 44 publications

(90 reference statements)

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“…These findings are consistent with recently published data demonstrating a higher number of vascular sprouts to occur at locations of low shear stress in self‐organized capillary networks in PDMS chips. [ 43 ] These findings also demonstrate the potential of our system for modeling complex events in cancer biology in vitro at the mesoscopic scale.…”

Section: Resultsmentioning

confidence: 59%

Engineering Mesoscopic 3D Tumor Models with a Self‐Organizing Vascularized Matrix

De Lorenzi,

Hansen,

Theek

et al. 2023

Advanced Materials

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Advanced in vitro systems such as multicellular spheroids and lab‐on‐a‐chip devices have been developed, but often fall short in reproducing the tissue scale and self‐organization of human diseases. We here introduce a bio‐printed artificial tumor model with endothelial and stromal cells self‐organizing into perfusable and functional vascular structures. Our model uses 3D hydrogel matrices to embed multicellular tumor spheroids, allowing them to grow to mesoscopic scales and to interact with endothelial cells. We show that angiogenic multicellular tumor spheroids promote the growth of a vascular network, which in turn further enhances the growth of co‐cultivated tumor spheroids. The self‐developed vascular structure infiltrates the tumor spheroids, forms functional connections with the bioprinted endothelium, and can be perfused by erythrocytes and polystyrene microspheres. Moreover, cancer cells migrate spontaneously from the tumor spheroid through the self‐assembled vascular network into the fluid flow. Additionally, tumor type specific characteristics of desmoplasia, angiogenesis, and metastatic propensity are preserved between patient‐derived samples and tumors derived from this same material growing in our bioreactors. Overall, our modular approach opens up new avenues for studying tumor pathophysiology and cellular interactions in vitro, providing a platform for advanced drug testing while reducing the need for in vivo experimentation.This article is protected by copyright. All rights reserved

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Section: Resultsmentioning

confidence: 59%

Engineering Mesoscopic 3D Tumor Models with a Self‐Organizing Vascularized Matrix

De Lorenzi,

Hansen,

Theek

et al. 2023

Advanced Materials

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“…Pericytes exist around microvessels and play a role in regulating blood flow and angiogenesis. 20 , 21 , 43 We for the first time reported the presence of pericyte in human IA tissue. Pericytes were marked by ABCC9 and KCNJ8 and uniquely expressed HIGD1B (Pct.1=79.5%, Pct.2=1.9%, log 2 FC=1.63) (Figure 1B ), in line with previous findings.…”

Section: Resultsmentioning

confidence: 89%

“… 45 We found that endothelial cells and pericytes interacted through PDGFB‐PDGFRB and TGFB1/3‐TGFBR2 pathways (Figure S2D through S2F ), corroborating the role of pericytes in neovascularization and sprouting. 43 , 46 …”

Section: Resultsmentioning

confidence: 99%

Decoding the Cell Atlas and Inflammatory Features of Human Intracranial Aneurysm Wall by Single‐Cell RNA Sequencing

Ji,

Li,

Sun

et al. 2024

JAHA

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Background Intracranial aneurysm (IA) is common and occasionally results in life‐threatening hemorrhagic strokes. However, the cell architecture and inflammation in the IA dome remain less understood. Methods and Results Single‐cell RNA sequencing was performed on ruptured and unruptured human IA domes for delineating the cell atlas, gene expression perturbations, and inflammation features. Two external bulk mRNA sequencing–based data sets and serological results of 126 patients were collected for validation. As a result, a total of 21 332 qualified cells were captured. Vascular cells, including endothelial cells, smooth muscle cells, fibroblasts, and pericytes, were assigned in extremely sparse numbers (4.84%), and were confirmed by immunofluorescence staining. Pericytes, characterized by ABCC9 and HIGD1B , were identified in the IA dome for the first time. Abundant immune cells were identified, with the proportion of monocytes/macrophages and neutrophils being remarkably higher in ruptured IA. The lymphocyte compartment was also thoroughly categorized. By leveraging external data sets and machine learning algorithms, macrophages were robustly associated with IA rupture, irrespective of their polarization status. The single nucleotide polymorphism rs2280543, which is identified in East Asian populations, was associated with macrophage metabolic reprogramming through regulating TALDO1 expression. Conclusions This study provides insights into the cellular architecture and inflammatory features in the IA dome and may enlighten novel therapeutics for unruptured IA.

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“…4D and E), which is in accordance with recent studies on vessels formed only by HUVECs and pericytes. 31,53 Culturing microvascular networks with a 1 : 1 to 1 : 2 PC-to-EC ratio resulted in very small diameters and the networks were not perfusable anymore. As expected, collagen IV immunostaining also revealed increased deposition of the ECM protein in the basal lamina surrounding the microvessels with higher PC ratios (Fig.…”

Section: Resultsmentioning

confidence: 99%

Self-assembled and perfusable microvasculature-on-chip for modeling leukocyte trafficking

Hirth,

Cao,

Peltonen

et al. 2024

Lab Chip

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Pericytes and shear stress each alter the shape of a self-assembled vascular network

Abstract: Blood vessel morphology is dictated by mechanical and biochemical cues. Among these, flow-induced shear stress and pericytes have been studied using an on-chip vascular network, for understanding the relationship between...

Cited by 11 publications

References 44 publications

Engineering Mesoscopic 3D Tumor Models with a Self‐Organizing Vascularized Matrix

Engineering Mesoscopic 3D Tumor Models with a Self‐Organizing Vascularized Matrix

Decoding the Cell Atlas and Inflammatory Features of Human Intracranial Aneurysm Wall by Single‐Cell RNA Sequencing

Self-assembled and perfusable microvasculature-on-chip for modeling leukocyte trafficking

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