TY - JOUR
KW - Experimental models of disease
KW - Regenerative Medicine
KW - Stem cells
KW - Stem-cell research
AU - Mattia Francesco Maria Gerli
AU - Giuseppe Calà
AU - Max Arran Beesley
AU - Beatrice Sina
AU - Lucinda Tullie
AU - Kylin Yunyan Sun
AU - Francesco Panariello
AU - Federica Michielin
AU - Joseph R. Davidson
AU - Francesca Maria Russo
AU - Brendan C. Jones
AU - Dani Do Hyang Lee
AU - Savvas Savvidis
AU - Theodoros Xenakis
AU - Ian C. Simcock
AU - Anna A. Straatman-Iwanowska
AU - Robert A. Hirst
AU - Anna L. David
AU - Christopher O’Callaghan
AU - Alessandro Olivo
AU - Simon Eaton
AU - Stavros P. Loukogeorgakis
AU - Davide Cacchiarelli
AU - Jan Deprest
AU - Vivian S. W. Li
AU - Giovanni Giuseppe Giobbe
AU - Paolo De Coppi
AB - Isolation of tissue-specific fetal stem cells and derivation of primary organoids is limited to samples obtained from termination of pregnancies, hampering prenatal investigation of fetal development and congenital diseases. Therefore, new patient-specific in vitro models are needed. To this aim, isolation and expansion of fetal stem cells during pregnancy, without the need for tissue samples or reprogramming, would be advantageous. Amniotic fluid (AF) is a source of cells from multiple developing organs. Using single-cell analysis, we characterized the cellular identities present in human AF. We identified and isolated viable epithelial stem/progenitor cells of fetal gastrointestinal, renal and pulmonary origin. Upon culture, these cells formed clonal epithelial organoids, manifesting small intestine, kidney tubule and lung identity. AF organoids exhibit transcriptomic, protein expression and functional features of their tissue of origin. With relevance for prenatal disease modeling, we derived lung organoids from AF and tracheal fluid cells of congenital diaphragmatic hernia fetuses, recapitulating some features of the disease. AF organoids are derived in a timeline compatible with prenatal intervention, potentially allowing investigation of therapeutic tools and regenerative medicine strategies personalized to the fetus at clinically relevant developmental stages.
BT - Nature Medicine
DA - 2024-03-04
DO - 10.1038/s41591-024-02807-z
LA - en
N2 - Isolation of tissue-specific fetal stem cells and derivation of primary organoids is limited to samples obtained from termination of pregnancies, hampering prenatal investigation of fetal development and congenital diseases. Therefore, new patient-specific in vitro models are needed. To this aim, isolation and expansion of fetal stem cells during pregnancy, without the need for tissue samples or reprogramming, would be advantageous. Amniotic fluid (AF) is a source of cells from multiple developing organs. Using single-cell analysis, we characterized the cellular identities present in human AF. We identified and isolated viable epithelial stem/progenitor cells of fetal gastrointestinal, renal and pulmonary origin. Upon culture, these cells formed clonal epithelial organoids, manifesting small intestine, kidney tubule and lung identity. AF organoids exhibit transcriptomic, protein expression and functional features of their tissue of origin. With relevance for prenatal disease modeling, we derived lung organoids from AF and tracheal fluid cells of congenital diaphragmatic hernia fetuses, recapitulating some features of the disease. AF organoids are derived in a timeline compatible with prenatal intervention, potentially allowing investigation of therapeutic tools and regenerative medicine strategies personalized to the fetus at clinically relevant developmental stages.
PY - 2024
SP - 1
EP - 13
T2 - Nature Medicine
TI - Single-cell guided prenatal derivation of primary fetal epithelial organoids from human amniotic and tracheal fluids
UR - https://www.nature.com/articles/s41591-024-02807-z
Y2 - 2024-03-05
SN - 1546-170X
ER -