Prenatal organoids for personalised medicine

Organoids are three-dimensional structures derived from a single stem cell. They self-organize in vitro and mature to recreate microarchitecture and characteristics of their tissues of origin. Since the first culture of mouse intestinal epithelial organoids and the translation to human, this technology has shown vast potential. Applications include developmental biology, disease modelling, drug testing and regenerative medicine making it increasingly relevant to clinical practice. Organoids can now be generated from tissues such as lung, intestine, kidney and brain using adult and fetal stem cells, pluripotent stem cells and cancer samples. Whether to study fetal development, disease physiopathology, regenerative medicine or to develop new therapies in a faster, more ethical and cost-effective way than animal models, organoids represent a powerful new tool. First described in 1999, personalised medicine aims to fine-tune diagnostic, prognosis and treatment to each patient. Nowadays, personalised medicine is spreading to most areas of clinical management, becoming the gold standard for the adoption of new interventions. More recently, these concepts have been applied to fetal medicine for prevention and therapy with initial reports appearing in literature in 2020. By recapitulating patient-specific disease mechanisms, prenatal organoids represent a unique bridge between in vitro-based approaches and personalised fetal medicine. This review presents fetal diseases for which organoids were explored, focusing on the implications of their derivation from prenatal sources such as the amniotic fluid, and discusses their advantages, challenges, and perspectives for prenatal counselling, prognosis or diagnosis, regenerative therapy, in utero surgery, disease modelling and prenatal drug testing.