Nordic Life Science 1
NASAL ORGANOIDS // PRECLINICAL SYSTEMS Growing tw
o or three-dimensional human nasal tissue can lead to better reliability in research studies, personalized treatment strategies, and ultimately contribute to better outcomes for patients. T E X T B Y MA L I N O T MA N I M ARIE HAGBOM, Docent, affiliated with Linköping University and Karolinska Institutet– Danderyd’s Hospital, is very familiar with organoids and their emerging potential. Organoids are spherical, three-dimensional tissue structures derived from stem cells that self-organize to mimic the structure and function of real organs. Having worked with nasal and intestinal organoids, and now also establishing lung organoids, Marie Hagbom believes this technology has the potential to transform biomedical research. “In the future, these models may replace many of the cancer cell lines and animal models currently used, offering more accurate and human-relevant results,” she says, citing an example from the COVID-19 pandemic. “During the pandemic, hydroxychloroquine was used as a treatment. Although it was initially considered to have antiviral activity in transformed monkey kidney cells (Vero cells), it did not reduce mortality or improve clinical outcomes in patients, nor did it show efficacy in human organoids. Similarly, chloroquine demonstrates broad antiviral activity across multiple viruses in transformed cell lines but shows minimal or no effect in human organoids. In contrast, the opposite pattern is observed with camostat mesylate for the treatment of SARS-CoV-2; it has weak or no effect in Vero cells but shows significant activity in human organoid models. Transformed cells tend to favor endosomal entry pathways, exhibit defective interferon responses, and often misrepresent human drug metabolism,” she explains. Powerful preclinical systems When it comes to the nose, Hagbom and her colleagues at the Department of Biomedical and Clinical Sciences at Linköping University, were one of the few groups in Europe able to collect and grow human adult nasal stem cells and induce them to form the different cell types of nasal epithelium. B y performing a simple nasal wash with saline and using a nasal swab, we can collect enough stem cells to grow them in culture and expand them as organoids, explains Hagbom. “These nasal organoids can be expanded, frozen, or differentiated into 3D nasal tissue. They can also be dissociated and plated in Transwells, where they form a 2D layer of nasal epithelium.” This nasal tissue has several advantages according to Hagbom. The stem cells can generate all the different cell NORDICLIFESCIENCE.ORG | 87