Researchers at the Boston University’s Center for Regenerative Medicine (CReM) and Boston Medical Center have developed a new method of growing intestinal organoids in vitro for use in disease research and drug screening.
The intestinal organoids were grown from donated human induced pluripotent stem cells (IPSCs), to which growth factors were added to trigger differentiation into intestinal cells. The intestinal organoids are three-dimensional groups of epithelial cells grown in a hydrogel.
In contrast to other methods of developing intestinal organoids, the organoids lack mesenchyme and consist solely of epithelial cells – the cells that are present in the intestinal tract. These organoids have allowed the researchers to develop accurate disease models which can be used to test the effectiveness of different drugs or treatments that target specific genetic defects. The organoids can be used to test treatments for a range of different diseases of the gut, including inflammatory bowel disease and colon cancer.
When creating the organoids, the researchers used CRISPR to create an IPSC cell line that glowed green when the stem cells differentiated into epithelial cells, allowing the researchers to see how the stem cells differentiated in vitro.
To demonstrate the potential of their intestinal organoids for use in drug development and disease research, the researchers created an intestinal organoid using IPSCs from donors with cystic fibrosis. The cells in the organoid contained the genetic mutation that causes cystic fibrosis, which was subsequently corrected using CRISPR.
Since it is possible for IPSCs to be expanded indefinitely, there is potential to scale up the production of the intestinal organoids for drug screening purposes.
“I hope that this study helps move forward our collective understanding about how diseases impact the gastrointestinal tract at the cellular level,” said Gustavo Mostoslavsky, MD, PhD, co-director of CReM and associate professor of medicine and microbiology at Boston University School of Medicine. “The continual development of novel techniques in creating highly differentiated cells that can be used to develop disease models in a lab setting will pave the way for the development of more targeted approaches to treat many different diseases.”
You can read more about the study in the paper – Generation of mesenchyme free intestinal organoids from human induced pluripotent stem cells – which was recently published in the journal Nature Communications. DOI: 10.1038/s41467-019-13916-6