Therapeutic and Toxicological Inhibition of Vasculogenesis and Angiogenesis Mediated by Artesunate, a Compound with Both Antimalarial and Anticancer Efficacy

Li, Qigui; Hickman, Mark; Weina, Peter J.

doi:10.5772/25934

Cited by 1 publication

(1 citation statement)

References 120 publications

(192 reference statements)

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“…This multicellular morphogenetic process is regulated by a different set of genes, leading to the formation of new blood vessels sprouting from pre-existing ones [9]. Angiogenesis builds capillaries from arteries and veins, thereby establishing the circulatory connections initiated by vasculogenesis [10]. To date, multiple studies have tried to mimic the role of vascular network structures using two-dimensional (2D) substrates, 3D gels, and microfluidic devices [7,[11][12][13].…”

Section: Introductionmentioning

confidence: 99%

Three-Dimensional Vascularized Lung Cancer-on-a-Chip with Lung Extracellular Matrix Hydrogels for In Vitro Screening

Park

Kim

et al. 2021

Cancers

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Recent advances in immunotherapies and molecularly targeted therapies have led to an increased interest in exploring the field of in vitro tumor mimetic platforms. An increasing need to understand the mechanisms of anti-cancer therapies has led to the development of natural tumor tissue-like in vitro platforms capable of simulating the tumor microenvironment. The incorporation of vascular structures into the in vitro platforms could be a crucial factor for functional investigation of most anti-cancer therapies, including immunotherapies, which are closely related to the circulatory system. Decellularized lung extracellular matrix (ldECM), comprised of ECM components and pro-angiogenic factors, can initiate vascularization and is ideal for mimicking the natural microenvironment. In this study, we used a ldECM-based hydrogel to develop a 3D vascularized lung cancer-on-a-chip (VLCC). We specifically encapsulated tri-cellular spheroids made from A549 cells, HUVECs, and human lung fibroblasts, for simulating solid type lung cancer. Additionally, two channels were incorporated in the hydrogel construct to mimic perfusable vessel structures that resemble arterioles or venules. Our study highlights how a more effective dose-dependent action of the anti-cancer drug Doxorubicin was observed using a VLCC over 2D screening. This observation confirmed the potential of the VLCC as a 3D in vitro drug screening tool.

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