Angiogenesis goes computational – The future way forward to discover new angiogenic targets?

Subramanian, Abhishek; Zakeri, Pooya; Mousa, Mira; Alnaqbi, Halima; Alshamsi, Fatima Yousif; Bettoni, Leo; Damiani, Ernesto; Alsafar, Habiba; Saeys, Yvan; Carmeliet, Peter

doi:10.1016/j.csbj.2022.09.019

Cited by 10 publications

(4 citation statements)

References 183 publications

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“…In contrast, in vitro and in vivo models involve the implantation of cancer cells into animal models, such as mice, to study tumor development and angiogenesis [89,90]. Although these models provide a more physiologically native tumor microenvironment, they are costly, time-consuming, and ethically challenging.…”

Section: Conventional Research Methods For Modeling Cancer Vasculogen...mentioning

confidence: 99%

Advancement in Cancer Vasculogenesis Modeling through 3D Bioprinting Technology

Shukla,

Yoon,

et al. 2024

Biomimetics

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Cancer vasculogenesis is a pivotal focus of cancer research and treatment given its critical role in tumor development, metastasis, and the formation of vasculogenic microenvironments. Traditional approaches to investigating cancer vasculogenesis face significant challenges in accurately modeling intricate microenvironments. Recent advancements in three-dimensional (3D) bioprinting technology present promising solutions to these challenges. This review provides an overview of cancer vasculogenesis and underscores the importance of precise modeling. It juxtaposes traditional techniques with 3D bioprinting technologies, elucidating the advantages of the latter in developing cancer vasculogenesis models. Furthermore, it explores applications in pathological investigations, preclinical medication screening for personalized treatment and cancer diagnostics, and envisages future prospects for 3D bioprinted cancer vasculogenesis models. Despite notable advancements, current 3D bioprinting techniques for cancer vasculogenesis modeling have several limitations. Nonetheless, by overcoming these challenges and with technological advances, 3D bioprinting exhibits immense potential for revolutionizing the understanding of cancer vasculogenesis and augmenting treatment modalities.

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Section: Conventional Research Methods For Modeling Cancer Vasculogen...mentioning

confidence: 99%

Advancement in Cancer Vasculogenesis Modeling through 3D Bioprinting Technology

Shukla,

Yoon,

et al. 2024

Biomimetics

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“…Even for converging pathways, differences in temporal regulation affect their signaling outcomes ( Jin et al, 2014 ). Computational models have been developed and provided important insights into understanding signaling pathways and cell-cell interactions ( Subramanian et al, 2022 ). For instance, Zhao et al designed an ordinary differential equation (ODE)-based computational model to understand hypoxia-responsive miRNAs control of the HIF-VEGF pathway in EC ( Zhao and Popel, 2015 ).…”

Section: Introductionmentioning

confidence: 99%

Endothelial cells signaling and patterning under hypoxia: a mechanistic integrative computational model including the Notch-Dll4 pathway

Oliveira,

Annex,

Popel

2024

Front. Physiol.

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Introduction: Several signaling pathways are activated during hypoxia to promote angiogenesis, leading to endothelial cell patterning, interaction, and downstream signaling. Understanding the mechanistic signaling differences between endothelial cells under normoxia and hypoxia and their response to different stimuli can guide therapies to modulate angiogenesis. We present a novel mechanistic model of interacting endothelial cells, including the main pathways involved in angiogenesis.Methods: We calibrate and fit the model parameters based on well-established modeling techniques that include structural and practical parameter identifiability, uncertainty quantification, and global sensitivity.Results: Our results indicate that the main pathways involved in patterning tip and stalk endothelial cells under hypoxia differ, and the time under hypoxia interferes with how different stimuli affect patterning. Additionally, our simulations indicate that Notch signaling might regulate vascular permeability and establish different Nitric Oxide release patterns for tip/stalk cells. Following simulations with various stimuli, our model suggests that factors such as time under hypoxia and oxygen availability must be considered for EC pattern control.Discussion: This project provides insights into the signaling and patterning of endothelial cells under various oxygen levels and stimulation by VEGFA and is our first integrative approach toward achieving EC control as a method for improving angiogenesis. Overall, our model provides a computational framework that can be built on to test angiogenesis-related therapies by modulation of different pathways, such as the Notch pathway.

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“…Decades of intense research, mostly using models of developmental angiogenesis, have led to the discovery of a plethora of angiogenic master regulators [ 2 , 3 ]. But undoubtedly, many genes that control EC behavior, fate, and/or EC interactions with other cells to ensure the generation of functional blood vessels still need to be described [ 9 ].…”

Section: Introductionmentioning

confidence: 99%

The vascular gene Apold1 is dispensable for normal development but controls angiogenesis under pathological conditions

et al. 2023

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The molecular mechanisms of angiogenesis have been intensely studied, but many genes that control endothelial behavior and fate still need to be described. Here, we characterize the role of Apold1 (Apolipoprotein L domain containing 1) in angiogenesis in vivo and in vitro. Single-cell analyses reveal that - across tissues - the expression of Apold1 is restricted to the vasculature and that Apold1 expression in endothelial cells (ECs) is highly sensitive to environmental factors. Using Apold1−/− mice, we find that Apold1 is dispensable for development and does not affect postnatal retinal angiogenesis nor alters the vascular network in adult brain and muscle. However, when exposed to ischemic conditions following photothrombotic stroke as well as femoral artery ligation, Apold1−/− mice display dramatic impairments in recovery and revascularization. We also find that human tumor endothelial cells express strikingly higher levels of Apold1 and that Apold1 deletion in mice stunts the growth of subcutaneous B16 melanoma tumors, which have smaller and poorly perfused vessels. Mechanistically, Apold1 is activated in ECs upon growth factor stimulation as well as in hypoxia, and Apold1 intrinsically controls EC proliferation but not migration. Our data demonstrate that Apold1 is a key regulator of angiogenesis in pathological settings, whereas it does not affect developmental angiogenesis, thus making it a promising candidate for clinical investigation.

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Angiogenesis goes computational – The future way forward to discover new angiogenic targets?

Cited by 10 publications

References 183 publications

Advancement in Cancer Vasculogenesis Modeling through 3D Bioprinting Technology

Advancement in Cancer Vasculogenesis Modeling through 3D Bioprinting Technology

Endothelial cells signaling and patterning under hypoxia: a mechanistic integrative computational model including the Notch-Dll4 pathway

The vascular gene Apold1 is dispensable for normal development but controls angiogenesis under pathological conditions

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