Organoids transplantation, the new model to speed up personalized medicine researches in Colon cancer and metastasis

Organoids are three dimensional in vitro culture systems derived from self-organizing stem cells. They can recapitulate the in vivo architecture functionality and genetic signature of original tissues. Researchers used CRISPR (which is consisting of a DNA-cutting enzyme called Cas9 and short RNA guide strands that target specific sequences of the genome, telling Cas9 where to make its cuts) to introduce cancer-causing mutations into the organoids and then delivered them via colonoscopy to the colon, where they attached to the lining and formed tumors. Once the tumors are established in the mice, the researchers can introduce additional mutations at any time, allowing them to study the influence of each mutation on tumor initiation, progression and metastasis. In human patients, mutations never occur all at once. Mutations are acquired over time as the tumor progresses and becomes more aggressive, invasive and metastatic. Now we can model these mutations in mice by using the organoid transplantation model. To demonstrate this ability, researchers delivered organoids with a mutated form of the APC gene, which is the cancer-initiating mutation in 80 percent of colon cancer patients. Once the tumors were established, they introduced a mutated form of KRAS, which is commonly found in colon and many other cancers. Furthermore, they delivered components of the CRISPR system directly into the colon wall to not only quickly model colon cancer by editing the APC gene, but also to edit the gene for P53, which is frequently mutated in colon and other types of cancers. The researchers’ further investigations showed that they could grow tumor cells from patients into organoids that could be transplanted into mice. This could give doctors a way to perform personalized medicine in which they test various treatment options against a patient s own tumor cells. Thus, this approach provides a fast and flexible means to produce tailored CRC mouse models for genetic studies and pre-clinical investigation

کلیدواژه ها:

Organoid ، CRISPR ، Colorectal cancer ، Personalized medicine