Presentation Details
| New approach methodologies in olfactory dysfunction: human organoids as a species-specific in vitro model Jennifer E.Douglas1, 2, Ankit Chauhan1, Kang-Hoon Kim2, Danielle R.Reed2, Noam A.Cohen1, 2, 3, Peihua Jiang2, Hong Wang2. 1University of Pennsylvania, Department of Otorhinolaryngology - Head & Neck Surgery, Philadelphia, PA, USA.2Monell Chemical Senses Center, Philadelphia, PA, USA.3Philadelphia Veterans Affairs Medical Center Surgical Services, Philadelphia, PA, USA |
Abstract
Olfactory dysfunction (OD) is common and has implications for safety, quality of life, and nutrition. Mouse models have been foundational in the study of OD; however, differences between mouse and human olfactory epithelium (OE) limit the translatability of results. Recent NIH guidance encourages a shift from animal to human-specific models in research, and organoids represent a New Approach Methodology (NAM) that can support this progress. We have developed a human olfactory organoid model using superior turbinate biopsies (which are positive for olfactory genes and proteins, indicating the presence of OE). Dissociated cells generate olfactory organoids when cultured in supplemented media, and the resulting organoids express key OE genes and proteins. They also contain cells with the characteristic appearance of olfactory sensory neurons (OSNs), which are responsible for transducing chemical information to the brain. As a control, organoids cultured from non-OE tissue do not express these markers. The olfactory organoids also show activation in response to select odorants, a surrogate of OSN function. Next, it will be important to determine whether cultures respond to the same complement of odorants as the human nose. It will also be crucial to mimic the OE microenvironment by co-culturing the organoids with immune cells. Drawing on our expertise in the diverse chemical structures of odorants, we plan to assess class-specific odorant response to better understand how well this model represents human olfaction. This human olfactory organoid NAM represents a promising step forward in the study of human olfaction and can be optimized for downstream studies to provide insight for diagnostic and therapeutic purposes.
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No part of this publication may be reproduced, distributed, or transmitted in any form or by any means, including photocopying, recording, or other electronic or mechanical methods, without the prior written permission of the author.