Part 13. B cell lymphoma patient derived lymph node organoids in GrowDex^®-T

B cell lymphomas are a group of aggressive hematologic malignancies, where the patients, due to disease heterogeneity, have a high risk of relapse and treatment resistance (40-60%). Thus, new medication to combat uncontrolled growth, are needed. Patient biopsies grown in 3D cultures present a promising strategy for a large-scale drug screening to improve the current treatment strategies. As a step towards this goal, we have developed a patient-derived lymphoma model using Growdex-T nanocellulose hydrogel.

In this project, patient lymph node fresh tissue samples were collected and processed with gentle mechanical dissociation to isolate B and T cells, and cultured in GrowDex-T hydrogel with medium for human B cell expansion for 7-21 days. The animal product-free nanocellulose fibers support the non-adherent immune cells in a compact organoid structure. We studied hallmark molecular pathways in B cell lymphomas in response to treatment, such as B cell activation signalling, cell hyperproliferation and survival. Organoids were imaged during the entire culturing period in a live imaging system to evaluate tumor outgrowth and progression rate, then collected for Western Blotting, FACS analysis, and immunocytochemistry staining.

The intact ratio of immune cells in patients’ lymph node maintain the microenvironment of the cancerous tissue, ideal for organoids without the need for complicated co-cultures. Such model is highly cost-efficient, reproducible and robust, with minimizing variation that arises from extensive experimental setup present in current solutions for lymph node organoids. We conclude that this model has a great potential as an ex vivo drug testing platform from patients’ own malignant tissue, and represents a straightforward solution towards personalized medicine.

Jelena Gnjatovic is a doctoral researcher in the subject of Clinical oncology, Doctoral programme in Clinical Research, University of Turku. She is working in Saara Hämälistö's research group 'Intercellular communication', founded in 2023. Jelena's doctoral project focuses on B cell lymphoma treatment by targeting lysosomes with repurposed drugs. They have developed a lymphoma organoid model in Growdex-T to study treatment responses in patients' lymph node biopsies in a highly reproducible and physiologically relevant manner. Jelena is experienced in confocal fluorescence microscopy and in 2D and 3D cell culturing of primary cells and cell lines.

Webinar includes a Q&A session