hPSC-derived lung and intestinal organoids as models of human fetal tissue

•Human induced and embryonic stem cells can generate complex 3-dimensional organ-like tissues (organoids).•Organoids grown in vitro are similar to immature, fetal tissue than adult tissue.•Immature organoids uniquely poises them to study human development and tissue maturation.•We review diseases that affect premature infants for which organoids may be a useful model.

In vitro human pluripotent stem cell (hPSC) derived tissues are excellent models to study certain aspects of normal human development. Current research in the field of hPSC derived tissues reveals these models to be inherently fetal-like on both a morphological and gene expression level. In this review we briefly discuss current methods for differentiating lung and intestinal tissue from hPSCs into individual 3-dimensional units called organoids. We discuss how these methods mirror what is known about in vivo signaling pathways of the developing embryo. Additionally, we will review how the inherent immaturity of these models lends them to be particularly valuable in the study of immature human tissues in the clinical setting of premature birth. Human lung organoids (HLOs) and human intestinal organoids (HIOs) not only model normal development, but can also be utilized to study several important diseases of prematurity such as respiratory distress syndrome (RDS), bronchopulmonary dysplasia (BPD), and necrotizing enterocolitis (NEC).