Title: Derivation of Vascularized Distal Lung Organoids from Human iPSC for Lung Development and Disease Modeling

Abstract:

Organoids have shown valuable progress for disease modeling and restating functional and morphological characteristics of the organs. However, most lung organoid studies have focused on human lung epithelial subtypes. They have not to date included human endothelial cells and systematically addressed the critical role of lung vascularization on lung development, homeostasis, and disease modeling. Here we have developed a human vascularized and functional lung organoid (hLO) system by co-culturing hPSC derived lung progenitors (LP) with either iPSC derived endothelial progenitor cells (iEC) or human lung microvascular endothelial cells (hLMVEC) to study mechanisms of human lung development and inflammatory lung injury. The co-culturing of either iEC or hLMVEC with LP plays an essential role in differentiation toward distal lung organoids by inducing distal lung markers gene expression, increasing the percentage of alveolar type II (AT2) cells, and inducing wnt signaling pathway. The co-culturing also increased the expression of ACE2 and protease TMPRSS2 and showed higher permissive to SARS-CoV-2 pseudovirus entry and this increase in the vascularized hLO was due to induction, especially in AT2 cells. Further, SARS-CoV-2 infection in hLO caused induction of different chemokines and cytokines including interferon signaling and in the vascularized hLO these inductions were more robust. This vascularized hLO undergo further structural and functional maturation and form functional blood vessels upon implantation into mouse kidney capsule and showed a massive influx of mouse neutrophils into vascularized hLO in response to the LPS challenge. Our vascularized hLO allows a new approach for studying human lung development and disease modeling for acute lung injury including COVID-19-disease.

Biography:

Abdul Qadir is a  Research assistant professor with in-depth knowledge and experience of stem cell, developmental biology, cancer, cancer stem cell, epigenetics, microRNA, and biomedical research. As a visiting assistant professor at the University of Illinois, his main focus is to develop iPSC-derived human vascularized lung organoids: for modeling homeostasis and Injury and resolution. During his postdoc at Northwestern University, he is focused on the mechanisms of Fas (CD95), a death receptor and Interferon mediated cancer stem cell formation. During his Ph.D., he has subsequently gained experience in the relationship between miRNA and Stem cell differentiation, especially towards osteogenesis, myogenesis, and adipogenesis.