Extracellular matrix hydrogel derived from decellularized tissues enables endoderm organoids culture

Organoids have extensive therapeutic potential and are increasingly opening up new avenues within regenerative medicine. However, the clinical application is greatly limited by the lack of effective GMP-compliant systems for organoid expansion in culture. Here, we envisage that the use of extracellular matrix hydrogels derived from decellularized tissues (DT) can provide an environment capable of directing cell growth. These gels possess the biochemical signature of tissue-specific ECM, and have the potential for clinical translation. Gels from decellularized porcine small intestinal mucosa/submucosa enable formation and growth of endoderm-derived human organoids, such as gastric, liver, pancreas, and small intestine. ECM gels could be used for direct organoids derivation from human biopsies, multiple passages with transcriptomic signature comparable to gold standard culture system, and in vivo organoid delivery. The development of these ECM-derived hydrogels opens up the potential for human organoids to be used clinically. We generated transcriptome data from human hepatocyte organoids (HepOrg) and human liver ductal organoids (DuctOrg) grown in standard BME hydrogel or newly developed ECM hydrogel purified from piglet liver ECM.