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Investigation of glioblastoma cell interaction with immune cell exosomes
Lithuanian University of Health Sciences
Laboratory of Pharmaceutical Sciences, Institute of Pharmaceutical Technologies, Faculty of Pharmacy, Medical Academy
Dr. Aistė Jekabšonė
Dr. Aistė Jekabšonė
Type of Research Project
- Basic science
What is the background of the project?
Over 80% of malignant brain tumours are gliomas, of which glioblastomas are the most invasive and have the worst survival prediction. Currently, there are no effective strategies for the treatment of glioblastoma, and surgical treatment combined with chemo-, immuno- and radiotherapy only delays, but does not stop the regeneration of these tumours. Glioblastoma aggressiveness is determined by the stem cell subpopulation resistance to chemotherapy and radiotherapy applied for this type of tumours, also tumour cell ability to migrate to tissues, which reduces the effectiveness of surgical and localized chemo/radiotherapy. Therefore, in order to achieve the effective treatment, it is necessary to develop new therapeutic strategies that enable the finding and destruction of both glioma stem cells and migrated glioblastoma cells that migrated from the primary tumour. The goal of this project is to apply immune cell exosomes that are capable of passing the blood-brain barrier and fuse with cancer cells as targeted drug delivery systems.
What is the aim of the project?
To investigate how exosomes from different immune cells (microglia, monocytes, NK-cells) interacts with glioblastoma cells in pure and mixed glioblastoma-brain cell (astrocytes, neurons) cultures.
What techniques and methods are used?
Exosomes will be isolated from cultivated immune cell medium by precipitation/multiple centrifugation steps (to eliminate debris and other macrovesicles) and gel filtration methods. They will be characterized by size and number by Zetasizer and according to surface markers by enzyme-linked immunosorbent assay (ELISA). Created systems will be tested in pure glioblastoma and mixed glioblastoma/brain cell cultures, and cell exosome fusion with cells as well as cell viability will be monitored by fluorescent microscopy: using a dye-fluorescence reagents which live cells can convert into a fluorescent end product.
What is the role of the student?
- The tasks of the student will be performed on his/her own
- The tasks will be done under supervision
- If the project includes “lab work”
- the student will take active part in the practical aspect of the project
What are the tasks expected to be accomplished by the student?
Immune, glioblastoma and brain cell cultivation, exosome isolation, characterisation, exosome staining, cell monitoring under brightfield and fluorescent microscope. Full participation in the laboratory will be expected. After the introduction to the SOPs, the student will start intensive laboratory training in cell culture and all exosome harvesting and investigation-related techniques. After a week of training, the individual goal and tasks will be set in detail, and the student will start on his/her own under the supervision. After one or two weeks of supervision, the student is expected to take his tasks independently with the consulting and advice when needed.
Will there be any theoretical teaching provided (preliminary readings, lectures, courses, seminars etc)
There will be no theoretical teaching provided.
What is expected from the student at the end of the research exchange? What will be the general outcome of the student?
- The student will prepare a poster - The student will prepare a presentation - The student will prepare a scientific report - The student’s name will be mentioned in a future publication
What skills are required of the student? Is there any special knowledge or a certain level of studies needed?
There are no specific practical skills required, however, it is expected that the student will dedicate as much time as he/she can for the project. We also expect that the student will attend at least 80% of the research exchange, be responsible for his/her actions at the practice and be accountable to the supervisor and LORE/NORE.
Are there any legal limitations in the student’s involvement
Type of students accepted
This project accepts: - Medical students - Graduated students (less than 6 months) - Pre-Medical students from the American-British system - Students in biomedical fields
- Gao; D. & Jiang; L. Exosomes in cancer therapy: a novel experimental strategy. Am. J. Cancer Res. 8; 2165–2175 (2018).
- Walker; N. D. et al. Exosomes from differentially activated macrophages influence dormancy or resurgence of breast cancer cells within bone marrow stroma. Cell Death Dis. 10; 1–16 (2019).
- Bellmunt; À. M.; López-Puerto; L.; Lorente; J. & Closa; D. Involvement of extracellular vesicles in the macrophage-tumor cell communication in head and neck squamous cell carcinoma. PLoS One 14; e0224710 (2019).
- Murgoci; A.-N. et al. Brain-Cortex Microglia-Derived Exosomes: Nanoparticles for Glioma Therapy. ChemPhysChem 19; 1205–1214 (2018).
- Golán; I.; De La Fuente; L. R. & Costoya; J. A. NK cell-based glioblastoma immunotherapy. Cancers (Basel). 10; (2018).
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