Open questions in human lung organoid research

Abstract

Organoids have become a prominent model system in pulmonary research. The ability to establish organoid cultures directly from patient tissue has expanded the repertoire of physiologically relevant preclinical model systems. In addition to their derivation from adult lung stem/progenitor cells, lung organoids can be derived from fetal tissue or induced pluripotent stem cells to fill a critical gap in modelling pulmonary development in vitro. Recent years have seen important progress in the characterisation and refinement of organoid culture systems. Here, we address several open questions in the field, including how closely organoids recapitulate the tissue of origin, how well organoids recapitulate patient cohorts, and how well organoids capture diversity within a patient. We advocate deeper characterisation of models using single cell technologies, generation of more diverse organoid biobanks and further standardisation of culture media.

Dysregulated cross-talk between alveolar epithelial cells and stromal cells in idiopathic pulmonary fibrosis reduces epithelial regenerative capacity

“…Organoid forming efficiency as an indication of regenerative capacity has been demonstrated for several other lung diseases ( 10 ). While fewer numbers of epithelial cells were isolated from the lungs from donors with IPF, our results show reduced numbers of organoids in IPF lung-derived cultures in the unfractionated groups independent of the number of epithelial cells.…”

“…A high mortality rate, while having no cure available, illustrates the urgent need to understand IPF pathogenesis to identify new therapeutic strategies (1). The origin of the disease is still unknown, Wisman et al 10.3389/fmed. 2023.1182368 Frontiers in Medicine 02 frontiersin.org but ongoing alveolar epithelial micro-injury and aberrant interactions within the stromal micro-environment are thought to induce the abnormal alveolar regeneration and tissue repair (2).…”

Anthrahydroquinone‑2,6‑disulfonate attenuates PQ‑induced acute lung injury through decreasing pulmonary microvascular permeability via inhibition of the PI3K/AKT/eNOS pathway

“…In recent years, organoid technology has become an indispensable model system in lung research. Besides being cultivated from adult lung stem/progenitor cells, lung organoids can also be derived from fetal tissue or induced pluripotent stem cells, greatly filling the technological gap in modelling lung development in vitro ( 50 ). With continuous technological advancements, significant progress has been made in the characterization and refinement of organoid culture systems ( 51 ).…”