Go With Your Gut

Your abdominal cavity contains many of the organs responsible for digestion, absorption, metabolism, and excretion. Together the break down the things we eat and drink so that they are available to all the cells of the body. Equally important, they help deal with the byproducts of metabolism in liver which helps with detoxification and the colon which helps eliminate solid waste. The interaction between the various organs and cell types the liver and colon the focus of research in both health and disease. Recently, two labs from the Cincinnati Children’s Hospital Medical Center have developed tools that will greatly benefit the study of these important organs.

                  In a letter to Nature, Camp et al have recapitulated liver development in vitro and produced small liver organoids from human induced pluripotent stem cells (iPSCs). These cells formed 3D tissues in culture when mixed with the appropriate cell types. Excitingly, these small organoid survived when implanted into mice. They also performed a genetic analysis of individual cells and found that these cells had many similarities to the gene expression of developing human liver cells.

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Figure 1: Researchers cultured iPSCs with other cell types in 2D and 3D cell culture systems (a). These 3D organoids were almost 1 cm in diameter (b). https://www.nature.com/nature/journal/v546/n7659/full/nature22796.html

                  The second group, Múnera et al. used human pluripotent stem cells to study the colon. The colon might seem fairly simple, but it is anything but. The study of 3D colon organoids had not been done before due to a lack of understanding of the proteins and genes involved in the development of this organ. They first performed a screening panel to determine which factors played the biggest role in this process. Surprisingly, they found that a protein normally involved in bone formation (bone morphogenic protein) was especially important. Using this discovery, they created 3D organoids of colon tissue that survived after implantation in mice.

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Figure 2: Spheroids of stem cells were placed in a gel and stimulated to form organoids.

http://www.sciencedirect.com/science/article/pii/S1934590917302266

                  These two studies demonstrate the versatility and the impact that stem cells are already making on research. These organoids are especially useful for studying organ development, but could also play a role in studying poorly understood diseases, such as Crohn’s disease of the GI tract. Additionally, they may be critical to developing and testing new drugs for a variety of diseases. Down the line, these discoveries may help us regenerate these organs for patients who need transplants due to accident or disease.