Current methods for isolating tissue-specific fetal stem cells and deriving primary organoids are limited to samples obtained post-pregnancy, hindering prenatal investigation. This study uses single-cell analysis of human amniotic fluid (AF) to identify and isolate viable epithelial stem/progenitor cells of fetal gastrointestinal, renal, and pulmonary origin. These cells formed clonal epithelial organoids exhibiting tissue-specific identities. Furthermore, lung organoids were derived from AF and tracheal fluid of fetuses with congenital diaphragmatic hernia (CDH), recapitulating disease features. This approach, compatible with prenatal intervention, offers potential for personalized fetal therapies and regenerative medicine.

Mattia Francesco Maria Gerli, Giuseppe Calà, Max Arran Beesley, Beatrice Sina, Lucinda Tullie, Kylin Yunyan Sun, Francesco Panariello, Federica Michielin, Joseph R. Davidson, Francesca Maria Russo, Brendan C. Jones, Dani Do Hyang Lee, Savvas Savvidis, Theodoros Xenakis, Ian C. Simcock, Anna A. Straatman-Iwanowska, Robert A. Hirst, Anna L. David, Christopher O'Callaghan, Alessandro Olivo, Simon Eaton, Stavros P. Loukogeorgakis, Davide Cacchiarelli, Jan Deprest, Vivian S. W. Li, Giovanni Giuseppe Giobbe, Paolo De Coppi