The increasing demand for organ transplantation has led many researchers to look for innovative ways to replace the need for human donors. Research in organoids, which are stem cell derived miniature mimics of organs typically grown in a dish, has significantly improved our understanding of organ development and structural organization. However, their size and simplicity has restricted organoid use to disease modeling and drug testing, limiting their potential for use in a transplantation setting. This is partly due to the fact that stem cells grown in a dish do not experience the same mechanical forces as they would in their native in vivo setting. Now a team of researchers led by Maxime Mahe from Cincinnati Children’s Hospital has figured out a way to simulate these mechanical forces, allowing them to grow larger, more complex, intestinal organoids.
Having previously demonstrated a method using a concoction of factors to grow human intestinal organoids in a dish, the team went on to transplant them into mice. However, to simulate the stretching and pulling that human intestinal tissues experience during development, the researchers followed the organoid with the implantation of a compressed spring encapsulated in a biodegradable polymer. This allowed for a delayed and slow deployment of the spring to better simulate the native strain our guts experience during growth. In addition to growing larger organoids (twice as large as those lacking springs) with morphology that more closely resembled native tissue (taller finger-like projections characteristic of intestinal tissues), the spring’s strain resulted in changes at the genetic level that better approximated those in human infant intestinal tissues.
While these organoids are a long way from implantation in a clinical setting, the successful use of external forces to better replicate in vivo growth conditions will certainly continue to be an active area of research to improve the quality and relevance of these models. More research will have to look at the ability of these organs to appropriately integrate with the recipient host, with particular consideration to the immune consequences of cross-species implantation of these engineered organs. The authors concluded their paper with a hint that studies in a larger animal model may soon follow.
Credit: CCHMC – Mahe Lab
The study in Nature Biomedical Engineering: Mechanically induced development and maturation of human intestinal organoids in vivo…
Some of the team’s past work: Functional human intestine grown from stem cells…
Top image: CCHMC – Wells/Helmrath labs