Matrigel, a mouse tumor-derived extracellular matrix (ECM), is crucial for organoid culture but has limitations. This study demonstrates that gastrointestinal (GI) tissue-derived ECM hydrogels are suitable Matrigel substitutes for GI organoid culture. Gastric and intestinal organoids grown in these hydrogels showed comparable or superior development and function compared to Matrigel. The hydrogels enabled long-term subculture and transplantation, providing tissue-mimetic microenvironments. Proteomic analysis revealed tissue-specific and age-related ECM profiles influencing organoid development. These GI tissue-derived ECM hydrogels offer an effective Matrigel alternative for disease modeling, drug development, and tissue regeneration.

Suran Kim, Sungjin Min, Yi Sun Choi, Sung-Hyun Jo, Jae Hun Jung, Kyusun Han, Jin Kim, Soohwan An, Yong Woo Ji, Yun-Gon Kim, Seung-Woo Cho