Using 3D-bioprinted models to study pediatric neural crest-derived tumors

Colin H. Quinn^1†, Andee M. Beierle^2†, Janet R. Julson¹, Michael E. Erwin¹, Hasan Alrefai², Hooper R. Markert¹, Jerry E. Stewart¹, Sara Claire Hutchins³, Laura V. Bownes¹, Jamie M. Aye³, Elizabeth Mroczek-Musulman⁴, Patricia H. Hicks⁴, Karina J. Yoon⁵, Christopher D. Willey^2*, Elizabeth A. Beierle^1*

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¹ Division of Pediatric Surgery, Department of Surgery, University of Alabama, Birmingham, Birmingham, AL, 35205, USA

² Department of Radiation Oncology, University of Alabama at Birmingham, Birmingham, AL, 35205, USA

³ Division of Pediatric Hematology Oncology, Department of Pediatrics, University of Alabama at Birmingham, Birmingham, AL, 35233, USA

⁴ Department of Pathology, University of Alabama at Birmingham, Birmingham, AL, 35233, USA

⁵ Department of Pharmacology and Toxicology, University of Alabama at Birmingham, Birmingham, AL, 35294, USA

IJB 2023, 9(4), 723 https://doi.org/10.18063/ijb.723

(This article belongs to the Special Issue Bioprinting process for tumor model development)

© Invalid date by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution 4.0 International License ( https://creativecommons.org/licenses/by/4.0/ )

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Abstract

The use of three-dimensional (3D) bioprinting has remained at the forefront of tissue engineering and has recently been employed for generating bioprinted solid tumors to be used as cancer models to test therapeutics. In pediatrics, neural crest-derived tumors are the most common type of extracranial solid tumors. There are only a few tumor-specific therapies that directly target these tumors, and the lack of new therapies remains detrimental to improving the outcomes for these patients. The absence of more efficacious therapies for pediatric solid tumors, in general, may be due to the inability of the currently employed preclinical models to recapitulate the solid tumor phenotype. In this study, we utilized 3D bioprinting to generate neural crest-derived solid tumors. The bioprinted tumors consisted of cells from established cell lines and patient-derived xenograft tumors mixed with a 6% gelatin/1% sodium alginate bioink. The viability and morphology of the bioprints were analyzed via bioluminescence and immunohisto chemistry, respectively. We compared the bioprints to traditional twodimensional (2D) cell culture under conditions such as hypoxia and therapeutics. We successfully produced viable neural crest-derived tumors that retained the histology and immunostaining characteristics of the original parent tumors. The bioprinted tumors propagated in culture and grew in orthotopic murine models. Furthermore, compared to cells grown in traditional 2D culture, the bioprinted tumors were resistant to hypoxia and chemotherapeutics, suggesting that the bioprints exhibited a phenotype that is consistent with that seen clinically in solid tumors, thus potentially making this model superior to traditional 2D culture for preclinical investigations. Future applications of this technology entail the potential to rapidly print pediatric solid tumors for use in highthroughput drug studies, expediting the identification of novel, individualized therapies.

Keywords

3D bioprinting

Neuroblastoma

Neuroendocrine; Pediatrics

Targeted therapy

Patient-derived xenografts

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International Journal of Bioprinting, Electronic ISSN: 2424-8002 Print ISSN: 2424-7723, Published by AccScience Publishing