Tissue extracellular matrix hydrogels as alternatives to Matrigel for culturing gastrointestinal organoids

TLDR

Matrigel, a mouse tumor‑derived extracellular matrix, is essential for organoid culture but impedes drug development and regenerative medicine due to its tumor origin, batch variability, high cost, and safety concerns. The study demonstrates that gastrointestinal tissue‑derived extracellular matrix hydrogels can replace Matrigel for culturing gastrointestinal organoids. Proteomic analysis revealed tissue‑specific and age‑related extracellular matrix profiles that influence organoid development. Organoids grown in tissue‑derived hydrogels exhibited development and function comparable or superior to Matrigel, enabled long‑term subculture and transplantation, and provide a suitable platform for disease modeling, drug testing, and tissue regeneration.

Abstract

Abstract Matrigel, a mouse tumor extracellular matrix protein mixture, is an indispensable component of most organoid tissue culture. However, it has limited the utility of organoids for drug development and regenerative medicine due to its tumor-derived origin, batch-to-batch variation, high cost, and safety issues. Here, we demonstrate that gastrointestinal tissue-derived extracellular matrix hydrogels are suitable substitutes for Matrigel in gastrointestinal organoid culture. We found that the development and function of gastric or intestinal organoids grown in tissue extracellular matrix hydrogels are comparable or often superior to those in Matrigel. In addition, gastrointestinal extracellular matrix hydrogels enabled long-term subculture and transplantation of organoids by providing gastrointestinal tissue-mimetic microenvironments. Tissue-specific and age-related extracellular matrix profiles that affect organoid development were also elucidated through proteomic analysis. Together, our results suggest that extracellular matrix hydrogels derived from decellularized gastrointestinal tissues are effective alternatives to the current gold standard, Matrigel, and produce organoids suitable for gastrointestinal disease modeling, drug development, and tissue regeneration.