Transcriptomic analysis of 3D vasculature-on-a-chip reveals paracrine factors affecting vasculature growth and maturation

Tan, Sin Yen; Jing, Qiuyu; Leung, Ziuwin; Xu, Ying; Cheng, Lily K.; Tam, Sindy Sing Ting; Wu, Angela Ruohao

doi:10.1039/d2lc00570k

Cited by 13 publications

(12 citation statements)

References 60 publications

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“…During early vascular development, VSMCs are recruited by endothelial cells to promote endothelial cell maturation and establish a stable vasculature through direct contact and paracrine regulation. 33,34 The fact that endothelial cell-specific deletion of SMAD4 causes a more severe effect than VSMC-KO of Smad4 does assert the subordinate role of VSMCs in regulating vascular development. 35 Intriguingly, here, we noticed that DDX24 depletion in VSMCs could cause the compromised cell proliferation (indicated by Ki67 staining) and vascular development in different milieus (ie, head, intersomitic vessel, and tail) of the embryos, as well as vascular remodeling in extra embryo.…”

Section: Discussionmentioning

confidence: 99%

DDX24 Is Essential for Cell Cycle Regulation in Vascular Smooth Muscle Cells During Vascular Development via Binding to FANCA mRNA

Gong

Liang

Liu

et al. 2023

ATVB

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BACKGROUND: The DEAD-box family is essential for tumorigenesis and embryogenesis. Previously, we linked the malfunction of DDX (DEAD-box RNA helicase)-24 to a special type of vascular malformation. Here, we aim to investigate the function of DDX24 in vascular smooth muscle cells (VSMCs) and embryonic vascular development. METHODS: CMC/VSMC-specific Ddx24 knockout mice were generated by crossing Tagln -Cre mice with Ddx24 flox/flox transgenic mice. The development of blood vessels was explored by stereomicroscope photography and immunofluorescence staining. Flow cytometry and cell proliferation assays were used to verify the regulation of DDX24 on the function of VSMCs. RNA sequencing and RNA immunoprecipitation quantitative real-time polymerase chain reaction were combined to investigate DDX24 downstream regulatory molecules. RNA pull-down and RNA stability experiments were performed to explore the regulation mechanism of DDX24. RESULTS: CMC/VSMC-specific Ddx24 knockout mice died before embryonic day 13.5 with defects in vessel formation and abnormal vascular remodeling in extraembryonic tissues. Ddx24 knockdown suppressed VSMC proliferation via cell cycle arrest, likely due to increased DNA damage. DDX24 protein bound to and stabilized the mRNA of FANCA (FA complementation group A) that responded to DNA damage. Consistent with the function of DDX24, depletion of FANCA also impacted cell cycle and DNA repair of VSMCs. Overexpression of FANCA was able to rescue the alterations caused by DDX24 deficiency. CONCLUSIONS: Our study unveiled a critical role of DDX24 in VSMC-mediated vascular development, highlighting a potential therapeutic target for VSMC-related pathological conditions.

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Section: Discussionmentioning

confidence: 99%

DDX24 Is Essential for Cell Cycle Regulation in Vascular Smooth Muscle Cells During Vascular Development via Binding to FANCA mRNA

Gong

Liang

Liu

et al. 2023

ATVB

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“…To construct the perfusable vascular network, collagen or fibrin gels from natural sources are often the choices because their interaction with ECs often results in vascular lumen formation. [189][190][191] In the unguided brain organoid forming procedures, Matrigel is used to support the expansion of the neuroepithelial buds. Pham et al used Matrigel to embed EC-coated brain organoids, which then led to robust vascularization.…”

Section: Extracellular Matrixmentioning

confidence: 99%

“…22,23 Third, microfluidics enables the generation of a perfusable vascular network for potential brain organoid vascularization. [24][25][26] Notably, accessible vascular lumens indicate the capability to allow delivery of substances, such as drugs or immune cells into the brain organoid. Given these advantages, there has been great interest in integrating microfluidics and organoid technologies.…”

Section: Introductionmentioning

confidence: 99%

Vascularized human brain organoid on-chip

et al. 2023

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“…Since previous microfluidic chips were generally semi-closed systems that required a destruction of chip to access the cells or a chemical cell lysis reagent for sample harvest, the confusion between different cell types was inevitable, making the process to be labor-extensive [31,67,68]. However, our open-top microfluidic chip allows direct access to the tumor samples, which reduce burden of sample harvest process and enable post-analysis aforementioned (e.g.…”

Section: Direct Harvest Of On-chip Tumor Samples and Secretome/gene E...mentioning

confidence: 99%

3D vascularized microphysiological system for investigation of tumor-endothelial crosstalk in anti-cancer drug resistance

Kim,

Park,

et al. 2023

Biofabrication

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Despite the advantages of microfluidic system in drug screening, vascular systems responsible for the transport of drugs and nutrients have been hardly considered in the microfluidic-based chemotherapeutic screening. Considering the physiological characteristics of highly vascularized urinary tumors, we here investigated the chemotherapeutic response of bladder tumor cells using a vascularized tumor on a chip. The microfluidic chip was designed to have open-top region for tumor sample introduction and hydrophilic rail for spontaneous hydrogel patterning, which contributed to the construction of tumor-hydrogel-endothelium interfaces in a spatiotemporal on-demand manner. Utilizing the chip where intravascularly injected cisplatin diffuse across the endothelium and transport into tumor samples, chemotherapeutic responses of cisplatin-resistant or -susceptible bladder tumor cells were evaluated, showing the preservation of cellular drug resistance even within the chip. The open-top structure also enabled the direct harvest of tumor samples and post analysis in terms of secretome and gene expressions. Comparing the cisplatin efficacy to the cisplatin-resistant tumor cells in the presence or absence of endothelium, we found that the proliferation rates of tumor cells were increased in the vasculature-incorporated chip. These have suggested that our vascularized tumor chip allows establishment of vascular-gel-tumor interfaces in spatiotemporal manners and further enables investigations of chemotherapeutic screening.

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Transcriptomic analysis of 3D vasculature-on-a-chip reveals paracrine factors affecting vasculature growth and maturation

Abstract: Transcriptomic studies of spatially arranged 3D vasculatures and fibroblasts revealed paracrine cues for improved vasculature growth.

Cited by 13 publications

References 60 publications

DDX24 Is Essential for Cell Cycle Regulation in Vascular Smooth Muscle Cells During Vascular Development via Binding to FANCA mRNA

DDX24 Is Essential for Cell Cycle Regulation in Vascular Smooth Muscle Cells During Vascular Development via Binding to FANCA mRNA

Vascularized human brain organoid on-chip

3D vascularized microphysiological system for investigation of tumor-endothelial crosstalk in anti-cancer drug resistance

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