Scientists have grown a model human esophagus using pluripotent stem cells for the first time.
- By precisely timing the application of different chemicals, scientists have grown a small, model esophagus from stem cells.
- They used the model esophagus to clarify why a certain congenital condition occurs.
- Using this technique, future researchers will be able to understand the nature of diseases better, develop new treatments, and even repair damaged esophagi.
Growing an esophagus<p>Developing this small esophagus organoid took a lot of precision. The 800-micrometer organoid was grown over the period of two months, but it started out as a slurry of pluripotent stem cells (PSCs). Unlike adult stem cells, which can only grow into specific, specialized types of tissues, PSCs can develop into any type of cell in the body. Essentially, they are our original components — every human started off as a similar slurry of PSCs.</p><p>The researchers exposed these cells to precise amounts of different chemicals that recreated the kind of events a PSC would undergo in order to develop into an esophagus in a normal developing fetus. These chemicals manipulated <a href="https://www.cancer.gov/publications/dictionaries/cancer-terms/def/signaling-pathway" target="_blank">cellular signaling pathways</a> — essentially, a chain of reactions that occur when a cell is exposed to a certain molecule. In the cell, a cascading series of reactions occurs that triggers some kind of event in a cell, such as cell death, replication, or, in this case, differentiation into esophagus cells.</p><p>Previous studies had tried to develop human esophagus organoids, but these usually ended up as a mixture of different tissues, including those found in the pharynx, the esophagus, and the respiratory tract. To develop esophageal tissues, the researchers needed to precisely time similarly precise quantities of chemicals to trigger the right signaling pathways for the right amount of time. </p><p>As an example, exposing the cells to retinoic acid for four days caused them to develop into tissues found lower down in the foregut, below the esophagus. Treating the cells in retinoic acid for just one day, however, seemed to be the right amount of exposure to encourage esophageal tissues to develop. In addition, treating the cells with Noggin — a curiously named protein — encouraged the tissues to develop into esophageal tissues rather than respiratory tissues.</p><img type="lazy-image" data-runner-src="https://assets.rebelmouse.io/eyJhbGciOiJIUzI1NiIsInR5cCI6IkpXVCJ9.eyJpbWFnZSI6Imh0dHBzOi8vYXNzZXRzLnJibC5tcy8xODY2OTAyNS9vcmlnaW4uanBnIiwiZXhwaXJlc19hdCI6MTYwOTAxMjk1NH0.lxKS_MUnCsvDIw4NPfyo8sXoMVSrounE3-jELCvqo2E/img.jpg?width=980" id="5d3a2" class="rm-shortcode" data-rm-shortcode-id="5cc12f694599c06332d61fb65b6f0e06" data-rm-shortcode-name="rebelmouse-image" />
A diagram depicting the various possible tissues the stem cells could have developed into. Exposing the cells to different molecules, such as retinoic acid (RA) and Noggin (NOG) encourages the stem cells to develop into different tissues.
Trisno et al., 2018