A bioengineered niche promotes in vivo engraftment and maturation of pluripotent stem cell derived human lung organoids

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 organo...

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Bibliographic Details
Published in:eLife 2016-09, Vol.5
Main Authors: Dye, Briana R, Dedhia, Priya H, Miller, Alyssa J, Nagy, Melinda S, White, Eric S, Shea, Lonnie D, Spence, Jason R
Format: Article
Language:English
Subjects:
Animals
Biomedical engineering
Biotechnology
Cell Differentiation
Cell proliferation
Developmental Biology and Stem Cells
Epithelium
Fetuses
human pluripotent stem cells
Humans
Lung
Lung - cytology
lung airway
Lung transplantation
Maturation
Medical research
Medical schools
Mice
Observations
Organoids
Organoids - cytology
Physiological aspects
Pluripotency
Pluripotent Stem Cells - physiology
Poly(lactide-co-glycolide)
Polyglactin 910 - metabolism
Research Advance
Respiratory tract
scaffolds
Smooth muscle
Stem cells
Tissue engineering
Tissue Scaffolds
Transplantation
Transplants & implants
Transplants - cytology
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Summary: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.
ISSN:2050-084X
2050-084X
DOI:10.7554/elife.19732