Graduate Student Yonsei University, Republic of Korea
Abstract: Esophageal organoids hold significant potential as therapeutics for esophageal mucosal damage, although their clinical application remains largely unexplored. To investigate esophageal organoids as regenerative therapeutics, there is an urgent need to develop alternatives to tumor-derived extracellular matrix (ECM), the standard culture matrix for organoids, due to its safety concerns. In this study, we leverage decellularized esophagus-derived ECM (EEM) for the culture and transplantation of esophageal organoids. Comprehensive proteomic analysis revealed that EEM provides a microenvironment with a complexity suitable for esophageal organoids. Furthermore, the reproducibility of EEM was confirmed by comparing proteomic profiles of EEM samples derived from different batches or donors. Esophageal organoids cultured in EEM hydrogel contained proliferative basal cells and differentiated suprabasal cells, similar to the structure of esophagus tissue. Additionally, the EEM hydrogel supported the long-term maintenance of esophageal organoids in vitro. The transplantation of esophageal organoids with EEM promoted epithelial regeneration and reduced fibrosis at the wound site in a mouse model of esophageal ulcer. Collectively, our EEM-based platform offers a stable and refined matrix, thereby advancing the clinical applications of esophageal organoids.
Funding Source: 1. The National Research Foundation of Korea (NRF) grant funded by the Ministry of Science and ICT (MSIT) (RS-2021-NR059722) 2. The Nano & Material Technology Development Program through the NRF funded by the MSIT (RS-2024-00449435)
