Extracellular matrix hydrogel derived from decellularized tissues enables endodermal organoid culture

TLDR

Organoids hold therapeutic promise but clinical use is limited by the lack of GMP‑compliant expansion systems. We propose using extracellular matrix hydrogels derived from decellularized tissues to create a growth‑directing environment. Hydrogels from decellularized porcine small intestine mucosa/submucosa support formation and growth of endodermal human organoids (gastric, hepatic, pancreatic, SI), maintain stable transcriptomes, enable direct derivation, and allow in vivo delivery, opening clinical potential.

Abstract

Organoids have extensive therapeutic potential and are increasingly opening up new avenues within regenerative medicine. However, their 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 (ECM) 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 intestine (SI) mucosa/submucosa enable formation and growth of endoderm-derived human organoids, such as gastric, hepatic, pancreatic, and SI. ECM gels can be used as a tool for direct human organoid derivation, for cell growth with a stable transcriptomic signature, and for in vivo organoid delivery. The development of these ECM-derived hydrogels opens up the potential for human organoids to be used clinically.