Page 321 - IJB-10-1

International Journal of Bioprinting 3D-bioprinted meningioma model

higher invasive ability, and higher level of difficulty stromal cells can be created using this technology, enabling
faced in treatment compared to benign meningiomas, studies of the interactions and signal transduction between
4
malignant meningiomas require a comprehensive different cell types during vascularization. 15-16 Moreover, 3D
treatment approach, such as surgery, radiation therapy, printing technology can be used to produce tumor models
and chemotherapy. However, given the complexity containing varying cell types for drug screening, which
5
of meningioma locations and the varying degree of can cater to drug exposure to different concentrations
malignancy, treatment effectiveness among patients varies and at different time points, thus simulating the realistic
17
substantially. Thus, suitable in vitro models for studying sensitivity and resistance of tumor drugs. Based on the
18
the molecular mechanisms of malignant meningiomas growth characteristics of meningiomas in the intracranial
and drug screening to aid in personalized treatments for cavity, we adopted a 3D coaxial construction model with
patients are urgently needed. freely flowing cavities that allows sufficient cell self-
Currently, established meningioma cell lines, assembly and can reproduce in vivo features. This method
including different subtypes such as malignant and benign is considered a promising technique for tumor model
meningiomas, are studied under two-dimensional (2D) construction. However, no studies have constructed a 3D
culture conditions. Conventional cell culture techniques model for meningiomas. Therefore, developing an in vitro
6
involving culture media, serum, and culture plates are model for meningiomas using 3D printing technology is a
typically used to maintain meningioma cell growth. suitable and effective strategy.
However, 2D culture of meningioma cells also has In this study, we employed 3D coaxial bioprinting
limitations and challenges. Under 2D culture conditions, to fabricate a 3D meningioma model. Our bioprinted
monolayer cells are forcibly flattened onto rigid surfaces, construct features a fibrous core-shell structure, where
lacking mutual contact between cells as well as uniform the unobstructed architecture of the inner core allows cell
exposure to nutrients and oxygen; thus, these conditions clustering and fusion into cell fibers, ultimately forming
fail to reflect the actual in vivo environment. Moreover, a complex 3D structure that resembles meningioma.
7-8
under 2D culture conditions, cells are usually in a static The outer shell is composed of biocompatible alginate,
state, which cannot fully simulate the microenvironment providing a supportive substrate for the containment and
and stress conditions in vivo. This phenomenon may growth of the inner core cell fibers. We first characterized
9
lead to changes in cell metabolism and function, thereby the structure of cell clustering within the inner shell and
affecting their role in tumor development and treatment. In assessed the effects of bioprinting on cell viability and
addition, 2D cell culture of tumor cells is suitable for in vitro proliferation. By using IOMM-Lee cells, we compared the
cell biology experiments and initial drug screening, but it expression levels of biological markers, cell invasion, and
has a low tumor formation rate and lacks the complexity epithelial–mesenchymal transition (EMT)-related protein
of tumor tissue. In recent years, the application of three- expression between 2D and 3D environments.
dimensional (3D) printing technology has provided new
possibilities for tumor research. In a 3D environment, cells Additionally, we evaluated the tumorigenicity of
not only possess 3D morphology but also undergo self- cells under different conditions using a subcutaneous
assembly through mutual contact between cells, better xenograft mouse model. Overall, we have successfully
recapitulating the true characteristics of in vivo tumors. 10-11 established an in vitro tumor model of meningioma that
3D printing technology can accurately reproduce the can faithfully recapitulate the biological characteristics and
structure and physiological characteristics of tumor tissue, microenvironment of this malignancy using 3D coaxial
substantially reducing the time required for animal model bioprinting technology (Figure 1).
construction while increasing tumorigenicity. This
12
method provides a more realistic in vitro research platform 2. Materials and methods
for tumor research. 2.1. Cell culture
In recent years, 3D printing technology has been The IOMM-Lee human meningioma cell line was
extensively applied in the construction of in vitro purchased from the American Type Culture Collection
tumor models to emulate realistic tumor biology and (ATCC). The cells were cultured in a 10 cm dish containing
microenvironments. For instance, 3D printing technology Dulbecco’s Modified Eagle Medium (DMEM; Gibco) with
can be employed to manufacture tumor spheroids 10% (v/v) fetal bovine serum (Gibco) and maintained at
composed of multiple cell types, thereby facilitating 37°C and 5% (v/v) CO . The medium was replaced every
13
2
investigations into the interactions and signal transduction 2 days, and the cells were observed for their condition
between different types of cells. 13-14 Additionally, and density. The collected cells were used for subsequent
vascularized tumor models containing endothelial and experiments.

Volume 10 Issue 1 (2024) 313 https://doi.org/10.36922/ijb.1342