Three-dimensionally reconstituted organoids that are just like human organs

December 18, 2020

Organoids are organ-like tissues 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. Recently, a research team in Korea introduced a new concept of mini-organs called assembloid that surpasses these organoids to structurally and functionally recapitulate human tissues. These findings were announced on December 17 (KST) in Nature, one of the most prestigious journals in science and technology.

A team led by Professor Kunyoo Shin of POSTECH's Department of Life Sciences has developed multi-layered miniature organs called assembloids that precisely mimic human tissues by three-dimensionally reconstituting stem cells together with various cell types in tissue stroma. The assembloid is a novel, innovative technology that can present a new paradigm for the next-generation drug discovery of intractable diseases as patient-customized human organs that transcend the conventional organoids.

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 a major issue in precisely modeling various intractable diseases including cancer.

To overcome these limitations, Shin's team developed reconstituted in-vitro human organs called assembloids, which have organized structures of epithelial cells, stromal layers, and outer muscle cells. The researchers found that these 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, the team 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 of solid cancers.

"These assembloids are the world's first in-vitro reconstituted organoids," explained Eunjee Kim, the first author of the paper. She added, "We can precisely model a variety of complex intractable diseases such as cancer, degenerative diseases, and various neurological diseases including schizophrenia and autism, and understand the pathogenesis of such diseases to ultimately develop better therapeutic options."

"To our knowledge, our efforts to generate assembloids that structurally and functionally recapitulate the pathophysiology of original tissues have not been previously described," commented Professor Shin who led the study. He added, "Generating 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."

Professor Tae-Young Roh, who contributed to the study, remarked, "This study is a great model for interdisciplinary science, and presents a new direction for precise and personalized therapy for various human diseases."
-end-
The research was conducted by Professor Shin and Eunjee Kim in the MS/Ph.D. program of POSTECH's Department of Life Sciences, and was supported by the Mid-Career Researcher Program, Brain Research Program, Regional Leading Research Center Program, and the Korea Post-Genome Project of the National Research Foundation of Korea. Professor Ja Hyun Koo of Seoul National University Hospital and POSTECH professors Sanguk Kim, Sungjune Jung, and Tae-Young Roh jointly contributed to the research.

Pohang University of Science & Technology (POSTECH)

Related Stem Cells Articles from Brightsurf:

SUTD researchers create heart cells from stem cells using 3D printing
SUTD researchers 3D printed a micro-scaled physical device to demonstrate a new level of control in the directed differentiation of stem cells, enhancing the production of cardiomyocytes.

More selective elimination of leukemia stem cells and blood stem cells
Hematopoietic stem cells from a healthy donor can help patients suffering from acute leukemia.

Computer simulations visualize how DNA is recognized to convert cells into stem cells
Researchers of the Hubrecht Institute (KNAW - The Netherlands) and the Max Planck Institute in Münster (Germany) have revealed how an essential protein helps to activate genomic DNA during the conversion of regular adult human cells into stem cells.

First events in stem cells becoming specialized cells needed for organ development
Cell biologists at the University of Toronto shed light on the very first step stem cells go through to turn into the specialized cells that make up organs.

Surprising research result: All immature cells can develop into stem cells
New sensational study conducted at the University of Copenhagen disproves traditional knowledge of stem cell development.

The development of brain stem cells into new nerve cells and why this can lead to cancer
Stem cells are true Jacks-of-all-trades of our bodies, as they can turn into the many different cell types of all organs.

Healthy blood stem cells have as many DNA mutations as leukemic cells
Researchers from the Princess Máxima Center for Pediatric Oncology have shown that the number of mutations in healthy and leukemic blood stem cells does not differ.

New method grows brain cells from stem cells quickly and efficiently
Researchers at Lund University in Sweden have developed a faster method to generate functional brain cells, called astrocytes, from embryonic stem cells.

NUS researchers confine mature cells to turn them into stem cells
Recent research led by Professor G.V. Shivashankar of the Mechanobiology Institute at the National University of Singapore and the FIRC Institute of Molecular Oncology in Italy, has revealed that mature cells can be reprogrammed into re-deployable stem cells without direct genetic modification -- by confining them to a defined geometric space for an extended period of time.

Researchers develop a new method for turning skin cells into pluripotent stem cells
Researchers at the University of Helsinki, Finland, and Karolinska Institutet, Sweden, have for the first time succeeded in converting human skin cells into pluripotent stem cells by activating the cell's own genes.

Read More: Stem Cells News and Stem Cells Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.