A physiologically relevant 3D collagen-based scaffold–neuroblastoma cell system exhibits chemosensitivity similar to orthotopic xenograft models

Abstract

Traditional 2D cell cultures do not completely capture the 3D architecture of cells and extracellular matrix contributing to a gap in our understanding of mammalian biology at the tissue level and may explain some of the discrepancies between in vitro and in vivo results. Here, we demonstrated the successful development and characterisation of a physiologically relevant, scaffold-based 3D tissue-engineered neuroblastoma cell model, strongly supporting its value in the evaluation of chemotherapeutics, targeted therapies and investigation of neuroblastoma pathogenesis. The ability to test drugs in this reproducible and controllable tissue-engineered model system will help reduce the attrition rate of the drug development process and lead to more effective and tailored therapies. Importantly, such 3D cell models help to reduce and replace animals for pre-clinical research addressing the principles of the 3Rs.

A three-dimensional bioprinted model to evaluate the effect of stiffness on neuroblastoma cell cluster dynamics and behavior

“…This study confirms the capacity of GelMA and different percentages of AlgMA scaffolds to support NB cell line growth, as previously described in the collagen-based scaffolds used by Curtin et al and Duarte Campos et al in their respective studies 51,52 . The stiffness properties of the printed hydrogels without bioinks, determined by Young's modulus as previously described, increased in line with AlgMA concentrations 43 , and no significant differences were found comparing the Young's modulus values of each stiffness at 37 °C or at room temperature, which confirms that all measurements carried out in human tumors, mice tumors and hydrogels are comparable at room temperature.…”

“…The challenge in treating HR-NB is gaining insight into structural, molecular and microenvironmental changes that can be applied to halt tumor metastasis and resistance to multiple chemotherapeutic drugs. 3D scaffold-based NB cell models have only recently been used in studies 51,52 yet provide valuable platforms for analyzing the biological signs underlying disease progression. In the present study we successfully characterized SK-N-BE(2) neuroblastic cell behavior in 3D culture, using bioprinted hydrogels composed from GelMA and different percentages of AlgMA to represent various ECM initial stiffness conditions.…”

Developing preclinical models of neuroblastoma: driving therapeutic testing

“…Scaffolded approaches have been used to model other cancer types, but limited scaffolded approaches have been utilized for NB. Curtin et al used lyophilized collagen I/glycosaminoglycan and collagen I/nanohydroxyapatite scaffolds for culturing of KELLY NB cells and a cisplatin-resistant KELLY cell derivative [169]. The NB cells exhibited reduced growth in 3D as compared to monolayer culturing, which is consistent with previously demonstrated results in other cancer cell lines [170,171].…”

“…Both 3D culture models exhibited similar chemosensitivity to the orthotopic in vivo model, with a reduced response observed as compared to the monolayer culture. Using these scaffolds, KELLY NB cells grown in 2D and 3D were used for evaluation of liposomes delivering miRNA for therapeutic gene silencing [169]. Unlike the chemotherapy studies, miRNA exhibited similar effects in 2D and 3D highlighting the potential usefulness of miRNA as a therapeutic.…”

Application of “Tissueoid Cell Culture System” Using a Silicate Fiber Scaffold for Cancer Research

“…Conventional 2-dimensional (2D) monolayer cell culture reportedly does not recapitulate the in vivo cancer microenvironment where cancer cells grow in a 3D manner [1]. 3D in vitro cell culturing is an innovative approach in cancer research to bridge the gap between conventional 2D culture and in vivo tumors [2]. Thus, many tools are now available for the development of in vitro 3D cultures [3].…”