Extracellular matrix hydrogel derived from decellularized tissues enables endoderm organoids culture

Organoids have huge 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-complaint systems for organoid expansion in culture. Here, we envisage that the use of extracellular matrix hydrogels derived from decellularized tissues (DT) can provide the instructive native environment necessary to direct cell growth. These gels possess the biochemical signature of tissue-specific ECM, and have the potential for clinical translation due to their natural, non-carcinogenic origin. We show that gels developed from decellularized porcine small intestinal mucosa have similar physiological range and mechanical properties to commercially available gels. ECM-derived gels enable formation and growth of endoderm-derived organoids and, moreover, supports in vivo organoid growth. The development of these ECM-derived hydrogels opens up the potential for human organoids to be used clinically. Overall design: RNA-seq profiles of organoids expanded on a decellularized porcine small intestinal mucosa-derived gel respect to control on Matrigel, with 4 replicates from the same pediatric small intestine cell line.