EXPERT REACTION: Fluid from around a growing baby could be used to grow organ-like structures

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Fluid from around a growing fetus could be used to create models of developing organs, including the kidney, lungs and small intestine, without having to terminate the pregnancy, according to international research. The researchers used fluid from the amniotic sac, which houses the developing baby within the womb, to collect stem cells which they then developed into 3D organ-like structures, called organoids. Using cells from a fetus with a condition called congenital diaphragmatic hernia, they were also able to create lung organoids with some of the features of this condition. This could allow researchers to develop specific therapies that are personalised to the growing fetus, as well as to better understand development during the later stages of pregnancy.

Journal/conference: Nature Medicine

Link to research (DOI): 10.1038/s41591-024-02807-z

Organisation/s: University College London, Great Ormand Street Hospital, UK

Funder: Research at Great Ormond Street Hospital NHS Foundation Trust
and UCL Great Ormond Street Institute of Child Health is made
possible by the NIHR Great Ormond Street Hospital (GOSH)
Biomedical Research Centre (BRC). M.F.M.G. held an H2020 Marie
Skłodowska-Curie Fellowship (843265, AmnioticID) and received
support from the Wellcome Institutional Strategic Support Fund,
UCL Global Engagement Fund, UCL Therapeutic Acceleration
Support (TAS Call 10) and the NIHR GOSH BRC. G.C. holds a UCL
Division of Surgery and Interventional Science PhD scholarship.
M.A.B. holds a GOSH Child Health Research Charitable Incorporated
Organization (GOSH-CC) PhD Studentship. L.T. holds an NIHR GOSH
BRC Crick Clinical Research Training Fellowship. K.Y.S. holds a PhD
Scholarship from Kidney Research UK (Paed_ST_005_220221129).
J.R.D. holds an MRC Clinical Research Training Fellowship
(MR/V006797/1). S.S. is a UKRI, EPSRC Doctoral Prize Fellow
(EP/T517793/1). A.O. is supported by the Royal Academy of Engineering
under the Chairs in Emerging Technologies scheme (CiET1819/2/78).
The work of D.C. is supported by the Fondazione Telethon Core Grant,
Armenise-Harvard Foundation Career Development Award, European
Research Council (759154, CellKarma) and the Italian Ministry of
Health (Piano Operativo Salute Traiettoria 3, ‘Genomed’). J.D. is funded
by the GOSH-CC. F.M.R. is supported by a grant from My FetUZ
at KU Leuven. B.C.J. is supported by the General Sir John Monash
Foundation as a Chairman’s Circle John Monash Scholar. A.L.D. is
supported by the UCLH BRC. V.S.W.L. is funded by the Francis Crick
Institute, which receives its core funding from Cancer Research UK
(CC2141), the UK MRC (CC2141) and the Wellcome Trust (CC2141).
G.G.G. is supported by the UCL Therapeutic Acceleration Support
LifeArc Fund Rare Diseases Call (TRO award no. 184646). G.G.G. and
S.P.L. are supported by the NIHR GOSH BRC. F.M. and P.D.C. are
supported by CDH-UK (16ICH03) and the BREATH Consortium
(Longfonds Voorhen Astma Fonds 552269). P.D.C. is also supported
by the NIHR (NIHR-RP-2014-04-046), H2020 (668294, INTENS), OAK
Foundation (W1095/OCAY-14-191), GOSH-CC (V5201), the Wellcome/
EPSRC Centre for Interventional and Surgical Sciences (WEISS),
University College London and NIHR GOSH BRC.

Media release

From: Springer Nature

Stem cells: Organoids created from amniotic fluid could model development in later-stage pregnancy *PRESS BRIEFING* 

Organoids of multiple different tissue types can be generated from cells collected from amniotic fluid samples, without termination of the pregnancy, reports a study published in Nature Medicine. The organoids may provide a means of understanding development during later-stage pregnancy and could aid research into congenital anomalies.

Organoids are three-dimensional models created from human stem cells that can resemble fetal-like tissue. Current methods for deriving organoids for modeling pregnancy — mostly from post-mortem fetal tissue — have legal and ethical implications and are usually available only up to 20–22 weeks after conception, which has limited research into development in the later stages of pregnancy.

Mattia Gerli, Paolo De Coppi, and colleagues evaluated epithelial cells from human amniotic fluid collected during prenatal investigations in 12 pregnancies between the 16th week and the 34th week. Using single-cell sequencing, the authors characterised the nature of the cells and identified and isolated epithelial cells of fetal gastrointestinal, renal and pulmonary origin. To explore if these cells could be used to create organoids, the authors seeded the cells in culture and observed that the cells began proliferating and self-organising into three-dimensional organoids, visible within two weeks. They found that the cells formed tissue-specific primary fetal organoids, namely, small intestine, kidney and lungs, and that they exhibited functional features of their origin tissue. The authors were able to use this technique to generate lung organoids from amniotic and tracheal fluid cells of fetuses affected by congenital diaphragmatic hernia that recapitulated some features of this condition.

Gerli, De Coppi, and colleagues suggest that their findings demonstrate an alternative method of generating fetal organoids without termination of pregnancy that addresses long-standing ethical concerns and could be used to study later gestational stages. They indicate that it may also offer the opportunity for autologous derivation of primary fetal organoids during ongoing pregnancies, which could enable the development of advanced prenatal models and personalized therapies and help improve parental counseling. They note that further studies are needed to validate the translational impact of these findings.

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