Advantages
- Simple culture media and process, no need to add special growth factors or small molecules to be added for fabrication.
- It is possible to produce organ primordia such as an autonomously beating heart, as well as neural tubes and intestinal tubes.
- Expected to differentiate into a variety of organs, but no structures corresponding to the brain or yolk sac are observed.
Technology Overview & Background
For drug efficacy and toxicity tests on human embryos, model organisms such as mice and cultured cells such as ES/iPS cells have been used, but these methods have limitations. For example, since there are significant differences between early development in humans and mice, the results obtained in mice do not necessarily apply to humans. Moreover, methods using cultured cells such as two-dimensionally cultured human ES/iPS cells are insufficient as methods for replacing complex biological tissues. Furthermore, although there are attempts to create organs from human ES/iPS cells and apply them to regenerative medicine, it is still difficult to create complex organs in vitro.
In this study, the researchers succeeded in developing an artificial embryo model containing organ primordia such as the heart by partially mimicking early human development using human iPS cells. Specifically, they discovered that by co-culturing primitive streak-like cells treated with a GSK3 inhibitor with iPS cells, they form co-aggregates, proliferate, and autonomously form embryo models. The obtained embryo models were confirmed to differentiate into organ primordia (cardiac, intestinal, neural tube, etc.), organs (blood vessels, etc.), neural tube, mesoderm, etc. without the use of any differentiation inducer in the manufacturing process.
Since this artificial human embryo model can autonomously form various organ primordia in an extremely simple process and medium, it is expected to be used in drug efficacy and toxicity tests targeting early embryos. And in the future, it is expected to be applied as organ primordia for organ transplantation. In addition, while differentiation into various organs is expected, differentiation into the brain and central nervous system has not been confirmed, and ethical issues are considered unlikely to arise.
Data
- It was found that by treating human iPS cells with a GSK3 inhibitor for 1–3 days to induce primitive streak-like cells, and then co-culturing them with undifferentiated iPS cells, the iPS cells and primitive streak-like cells form co-aggregates and elongate while proliferating.
- When the co-aggregates were transferred to a shaking incubator on days 3–4 of culture and the culture was continued, a heart-like structure, heart primordium, that beat was observed from around day 7. Differentiation of the neural tube and digestive tract were also confirmed at the same time. The heart is the earliest organ to be formed in the embryonic development process, and other organs (liver, lungs, kidneys, etc.) can be produced by extending the culture period.
Patent(s)
Patent pending (unpublished)
Principal Investigator & Academic Institution
Hiroaki Okae, DSc
Professor, Institute of Molecular Embryology and Genetics (IMEG), Kumamoto University (Japan)
Development Stage & Future Research Plans
- The artificial embryo model developed in this study can be further combined with gene modification technology to be used for creating congenital heart disease models.
- Since structures such as the intestinal tract and neural tube are also confirmed in this artificial embryo model in addition to the heart, if these organ primordia can be taken out and grown, application to organ transplantation can be greatly expected.
Expectations
TECH MANAGE is now looking for companies to collaborate with the researcher and develop this technology further under the licensing of the related patent.
- Use as an artificial human early embryo model for drug efficacy and toxicity tests targeting early embryos.
- Joint research for the production of organ primordia used for organ transplantation.
It is also possible to meet with the PI to discuss joint research using related invention(s), providing know-how based on confidentiality agreement (CDA), contracts for evaluation, and licensing options.
Project ID:JT-05163