Assistant Professor The University of Hong Kong, Hong Kong
Abstract: Human organoids derived from reprogrammed and tissue stem cells offer a valuable in vitro platform for studying human development, regeneration, and disease modeling. Current platforms mainly focus on generating airway epithelial cells from human ESCs and iPSCs but do not effectively translate complex communications across various cellular and tissue niches of the human airway. Moreover, there is a lack of consensus benchmarking standards across different organoid platforms and human samples. Addressing this knowledge and technological gap, we developed an improved method to create human airway organoids containing both epithelial and stromal lineages. We introduced a co-culture approach incorporating blood-circulating monocytes, leading to enhanced mesenchymal-epithelial crosstalk, the emergence of fetal-specific pulmonary neuroendocrine cells, and the differentiation of monocytes into self-sustaining alveolar macrophages. Using these complex organoids, we demonstrate the repair trajectory of airway progenitors upon viral infection and chemical-induced epithelial loss. In addition, we characterize the effect of inflammaging on airway repair mediated through macrophages derived from young and aged donors. Our analyses underscore the importance of constructing a complex signaling niche for a better understanding of human tissue regeneration, highlighting the potential of this research in translating discoveries into clinical applications.
