A bioengineered niche promotes in vivo engraftment and maturation of pluripotent stem cell derived human lung organoids
Briana R Dye,
Priya H Dedhia,
Alyssa J Miller,
Melinda S Nagy,
Eric S White,
Lonnie D Shea,
Jason R Spence
Affiliations
Briana R Dye
Department of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, United States
Priya H Dedhia
Department of Surgery, University of Michigan Medical School, Ann Arbor, United States
Alyssa J Miller
Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, United States; Program in Cellular and Molecular Biology, University of Michigan Medical School, Ann Arbor, United States
Melinda S Nagy
Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, United States
Eric S White
Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, United States
Lonnie D Shea
Center for Organogenesis, University of Michigan Medical School, Ann Arbor, United States; Biomedical Engineering, University of Michigan Biomedical Engineering, Ann Arbor, United States
Department of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, United States; Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, United States; Center for Organogenesis, University of Michigan Medical School, Ann Arbor, United States
Human pluripotent stem cell (hPSC) derived tissues often remain developmentally immature in vitro, and become more adult-like in their structure, cellular diversity and function following transplantation into immunocompromised mice. Previously we have demonstrated that hPSC-derived human lung organoids (HLOs) resembled human fetal lung tissue in vitro (Dye et al., 2015). Here we show that HLOs required a bioartificial microporous poly(lactide-co-glycolide) (PLG) scaffold niche for successful engraftment, long-term survival, and maturation of lung epithelium in vivo. Analysis of scaffold-grown transplanted tissue showed airway-like tissue with enhanced epithelial structure and organization compared to HLOs grown in vitro. By further comparing in vitro and in vivo grown HLOs with fetal and adult human lung tissue, we found that in vivo transplanted HLOs had improved cellular differentiation of secretory lineages that is reflective of differences between fetal and adult tissue, resulting in airway-like structures that were remarkably similar to the native adult human lung.
