PhD Scientific Days 2025

Poster Session II. - E: Pathological and Oncological Sciences

3D bioprinted glioma models: preclinical applications and drug sensitivity testing

Name of the presenter

Gelencsér Rebeka

Institute/workplace of the presenter

Department of Pathology and Experimental Cancer Research

Authors

Rebeka Gelencsér¹, Dorottya Moldvai¹, Dániel Sztankovics¹, Risa Miyaura¹, Fatime Szalai¹, Viktória Varga¹, Beáta Benkő¹, Ildikó Krencz¹, Anna Sebestyén¹

1: Department of Pathology and Experimental Cancer Research

Text of the abstract

Introduction: The treatment of central nervous system tumours, including gliomas, remains a major challenge today. The efficacy of the most commonly used chemotherapeutic agent, temozolomide (TMZ), is limited and new agents under development have not brought breakthroughs. Preclinical trials in inappropriate models may be behind several clinical trial failures. Changes in the metabolic processes that ensure cell growth and survival are difficult to model. These metabolic processes may differ significantly in conventional two-dimensional (2D) cell culture and in various three-dimensional (3D) in vitro models, which may contribute to significant differences in therapy resistance.
Aims: To investigate 3D bioprinted glioma tumour models in drug susceptibility testing, comparing 2D and 3D models.
Method: In our experiments, 3D bioprinted glioma tumour models (U373, U251) were created using GeSiM Bioscaffolder 3.2 bioprinter. The 3D bioprinted structures were maintained for three weeks. The drug sensitivity of 2D and 3D models (rapamycin/RAPA - 50 ng/ml, TMZ - 100 μM) was compared using proliferation assays (Alamar Blue, Sulforhodamine B). In vivo drug sensitivity was also tested in animal experiments (n = 7/group; RAPA – 3 mg/kg; TMZ – 50 mg/kg), following tumor size for three weeks and measuring final tumorweight.
Results: in 2D cell cultures both cell line were RAPA sensitive and TMZ resistant. In 3D, both treatments were ineffective on both cell lines. In combined treatment, we observed inhibition of proliferation in 2D cultures, but our 3D bioprinted models were more resistant. Our in vivo results using SCID mice showed resistance to TMZ, while sensitivity to rapamycin and combined treatment.
Conclusion: In our experiments, a decrease in therapeutic sensitivity was observed in 3D environment compared to 2D cell cultures. The differences in drug sensitivity observed in human phase studies may be due to different growing activity of tumor cells in 2D and 3D environments. Surprisingly our results in 3D bioprinted cultures instead in 2D cultures and xenograft model supported the fact that the combination of TMZ and rapalog has been shown to be unsuccessful in clinical trials. This highlights the importance of developing new 3D cell culture technologies to increase the efficiency of drug substance preselection studies.
Funding: EKÖP-2024-116 and NKFI-142799