Page 123 - IJB-9-4

International Journal of Bioprinting

RESEARCH ARTICLE
Using 3D-bioprinted models to study pediatric

neural crest-derived tumors

Colin H. Quinn , Andee M. Beierle , Janet R. Julson , Michael E. Erwin ,
1†
2†
1
1
Hasan Alrefai , Hooper R. Markert , Jerry E. Stewart , Sara Claire Hutchins ,
1
1
2
3
Laura V. Bownes , Jamie M. Aye , Elizabeth Mroczek-Musulman ,
3
1
4
Patricia H. Hicks , Karina J. Yoon , Christopher D. Willey *, Elizabeth A. Beierle *
4
2
1
5
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
(This article belongs to the Special Issue: Bioprinting process for tumor model development)
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
† These authors contributed equally to be used as cancer models to test therapeutics. In pediatrics, neural crest-derived
to this work. 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
*Corresponding authors:
Christopher D. Willey remains detrimental to improving the outcomes for these patients. The absence of
(cwilley@uabmc.edu) more efficacious therapies for pediatric solid tumors, in general, may be due to the
Elizabeth A. Beierle inability of the currently employed preclinical models to recapitulate the solid tumor
(elizabeth.beierle@childrensal.org) phenotype. In this study, we utilized 3D bioprinting to generate neural crest-derived
Citation: Quinn CH, Beierle AM, solid tumors. The bioprinted tumors consisted of cells from established cell lines and
Julson JR, et al., 2023, Using patient-derived xenograft tumors mixed with a 6% gelatin/1% sodium alginate bioink.
3D-bioprinted models to study
pediatric neural crest-derived The viability and morphology of the bioprints were analyzed via bioluminescence and
tumors. Int J Bioprint, 9(4): 723. immunohisto chemistry, respectively. We compared the bioprints to traditional two-
https://doi.org/10.18063/ijb.723 dimensional (2D) cell culture under conditions such as hypoxia and therapeutics. We
Received: December 17, 2022 successfully produced viable neural crest-derived tumors that retained the histology and
Accepted: February 21, 2023 immunostaining characteristics of the original parent tumors. The bioprinted tumors
Published Online: March 29, 2023
propagated in culture and grew in orthotopic murine models. Furthermore, compared
Copyright: © 2023 Author(s). to cells grown in traditional 2D culture, the bioprinted tumors were resistant to hypoxia
This is an Open Access article and chemotherapeutics, suggesting that the bioprints exhibited a phenotype that is
distributed under the terms of the
Creative Commons Attribution consistent with that seen clinically in solid tumors, thus potentially making this model
License, permitting distribution superior to traditional 2D culture for preclinical investigations. Future applications of this
and reproduction in any medium, technology entail the potential to rapidly print pediatric solid tumors for use in high-
provided the original work is
properly cited. throughput drug studies, expediting the identification of novel, individualized therapies.
Publisher’s Note: Whioce
Publishing remains neutral with Keywords: 3D bioprinting; Neuroblastoma; Neuroendocrine; Pediatrics; Targeted
regard to jurisdictional claims in
published maps and institutional therapy; Patient-derived xenografts
affiliations.

Volume 9 Issue 4 (2023) 115 https://doi.org/10.18063/ijb.723