Scaffolds Promote the Development and Growth of Organoids

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Organoids – miniature organs produced via stem cells which show three-dimensional, tissue-like arrangement – enable, through physiologically-relevant environments, the study of various pathologies which these structures are assembled for. Typically assembled devoid of scaffolds, organoids have been used for both drug discovery and as three-dimensional tissue engineered constructs. As tissue engineered assemblies, organoids have originally been formed on the basis of cultured stem cells, such as induced pluripotent stem cells, which rearrange, through spatially-restricted lineage committment, into layered structures.

In the last few years, studies have highlighted that organoids can be enhanced with the introduction of substrates to which cells adhere.

In 2016, a manuscript by Dr. Timothy O’Brien from the Stem Cell Institute at the University of Minnesota described the generation of cerebral organoids from human pluripotent stem cells with the support of a chemically defined hydrogel. They managed to achieve protein expression representative of forebrain, midbrain, and hindbrain development. The manuscript was published in Stem Cells Translational Medicine.

This was demonstrated again last week, when a new study appeared which described the development of scaffold-support human lung organoids. Authored by lab of Dr. Jason Spence at the University of Michigan Medical School, the manuscript, titled A bioengineered niche promotes in vivo engraftment and maturation of pluripotent stem cell derived human lung organoids, presented the development of microporous poly(lactide-co-glycolide) (PLG) scaffolds as substrated onto which human pluripotent stem cell-based organoids developed into maturate of lung epithelial tissue.

Upon transplanting scaffold-grown organoid tissue, airway-like epithelial tissue was observed. This was attributed to the enhanced support provided by the polymer-based support scaffolds.

 

elife-19732-fig4
From Dye et al., 2016.: Scaffold-Human Lung Organoid showed cartilage-dependent staning which was not present in control scaffold after 8 weeks of in vivo transplantation.

 

The authors argued that this study was the first demonstration of the development of hPSC-derived human lung organoids which showed robust engraftment in vivo and differentiation into an organized pseudostratified epithelium.

Organized cartilage was observed following Safranin0 stanining within the scaffold-human lung organoids following transplantation (Figure above), alongside cartilage marker SOX9, and the human mitochondrial marker huMITO. The scaffold-human lung organoid also displayed abundant vasculature within the tissue.

This manuscript, alongside previous other studies, forms a growing body of work which suggests that providing a physical environment to stem cell-based organoids, is critical in ensuring development and organization of mature tissue-like structure and function. Further developments may shed more light into the relationship between scaffold physicochemical properties and organoid-based human tissue establishment to develop more sophisticated system for organ regeneration.

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