Organoids are organ-like tissue derived from stem cells that are grown in labs, often referred to as miniature organs. Because they can imitate the structure and function of human organs, it is considered as the next-generation technology for creating artificial organs or developing new drugs. By three-dimensionally reconstituting stem cells together with various cell types in tissue stroma, our lab recently developed a new concept of mini-organ, called assembloid that structurally and functionally recapitulates the human tissues. These findings were published in journal Nature (https://rdcu.be/cckjo), one of the most prestigious journal in science and technology.
Organoids are miniature organs that are similar to human organs. However, the current organoid technology has a fundamental limitation in that they cannot mimic the mature structure of organs and lack the microenvironment within the tissues. Furthermore, critical interactions between various cells within the human tissues is lacking. This limitation has been considered as a big issue in precisely modeling various intractable diseases including cancer. To overcome these limitations, our team developed reconstituted in-vitro human organs called assembloids, which have organized structures of epithelial cells, stromal layers, and outer muscle cells. We found that assembloids were identical to mature adult organs in terms of cell composition and gene expression at the single cell level, and that they mimic the in-vivo regenerative response of normal tissues to the injury.
In addition, our lab developed patient-specific tumor assembloids that perfectly mimic the pathological characteristics of in vivo tumors. Using this tumor assembloid platform with genetic engineering technologies, the team revealed the novel mechanisms in which the signals from the tumor microenvironment determines the plasticity of the tumor cells. These findings show that the signaling feedback between the tumor and stromal cells play a critical role in controlling the tumor plasticity. This discovery will lead to a novel paradigm in the development of cell differentiation therapy for the treatment of various aggressive types solid cancers.
We believe that generation of such artificial tissues is particularly relevant to modern research because the importance of tissue microenvironments in epithelial tissue homeostasis and the growth of various tumors is increasingly being recognized. We anticipate our study to open a new era of a drug discovery that will revolutionize the advancement of patient-customized treatment for various intractable diseases.