Scientists culture parasites in mini-organs from the lab
Researchers from the research group of Hans Clevers have succeeded in growing a parasite in mini-organs in the lab. Until now, it was difficult to study the Cryptosporidium parasite, which causes severe diarrhea, in the laboratory. The scientists write this in an article published today in Nature Microbiology.
An infection with the Cryptosporidiumparasite can cause severe diarrhea. In healthy people with a functioning immune system, these symptoms disappear automatically. However, this is not always the case in AIDS patients, the elderly or in malnourished children. Cryptosporidiosis is therefore one of the largest causes of childhood mortality worldwide. However, currently too little is known about the parasite to develop a vaccine or an adequate medicine. This is mainly due to the lack of a good in-vitroculture system derived from healthy tissue that can mimic an infection with Cryptosporidiumoutside the human body.
The Utrecht researchers have now succeeded in establishing a breeding method for the malicious parasite. They did so with the help of organoids: mini-organs that consist of, for example, lung or intestinal tissue and are grown outside the human body from stem cells. Organoids consist of cells that have organized themselves in the same way as in organs and continue to live in the laboratory. Watch this animation of the life cycle of Cyclosporidium parvum in a gut organoid.
The scientists showed that Cryptosporidiumcan infect intestinal and lung organoids and propagate itself for long periods of time. The parasites completed their entire cycle in organoids and the newly produced oocysts were also able to infect new target cells, just like the oocysts that cause infection in the human body. Gene expression profiling showed an activation of genes involved in innate immune responses. Furthermore, the scientists could ascertain that the absorptive enterocytes are the cell type that are targeted by the parasite in the small epithelium.
According to the researchers, their method is a new way to study Cryptosporidiuminfection and will open avenues for similar host-microbe interactions studies using organoid cultures. They propose to combine their method with the genetic manipulation of the parasite, so that the different steps in the development can be studied even better.
Modeling Cryptosporidiuminfection in human small intestinal and lung organoids
Inha Heo, Devanjali Dutta, Deborah Schaefer, Nino Iakobachvili, Benedetta Artegiani, Norman Sachs, Kim Boonekamp, Gregory Bowden, Antoni Hendrickx, Robert Willems, Peter Peters, Michael Riggs, Roberta O’Connor, Hans Clevers
Nature Microbiology, DOI: http://dx.doi.org/10.1038/s41564-018-0177-8
Hans Clevers is professor of Molecular Genetics at the Utrecht University and University Medical Center Utrecht, and group leader at the Hubrecht Institute for Developmental Biology and Stem Cell Research. He is also Director Research of the Princess Máxima Center for Pediatric Oncology and Oncode Investigator.