What are Chimeras?
Chimeras are persons or animals that have some living cells in their body that came from another person or animal. Chimerism can occur in nature (for example a mother’s cells can be found in her child decades later, just as a child’s cells can remain in their mother), can be the result of a transplant (such as a bone marrow or organ transplantation from a human donor or tissue transplantation from an animal donor, such as a pig heart valve), or chimeric animals can be created in the lab as part of biomedical research.
Chimeras have been studied by scientists for decades. In the 1960s, scientists conducted pioneering work transplanting quail cells into a developing chick embryo, which provided groundbreaking insight into how cells contribute to specific systems, tissues, and structures. These chimeras went on to help inform our understanding of brain development, epilepsy, and other disorders. Chimeric embryos help scientists understand disease progression, identify new therapies, and may be a potential source of organs for transplantation in the future.
How is Research Involving Chimeras Applied to Improve Human Health?
While non-chimeric animals have been used to successfully model many human diseases, they cannot always replicate the human condition. Human-animal chimeras have been used for decades to better approximate how the human body works and identify new treatments for various diseases, examples include:
- Human cancer cells transferred into specialized mice help scientists explain how cancers spread and uncover new anti-cancer therapies.
- Mice engineered to have immune systems similar to humans allow scientists to study human immunity and autoimmune diseases and test new treatments for infectious diseases, including human-specific infectious diseases.
- Human-mouse chimeras reveal how certain organs are diseased and how the resulting disease can be treated, for example studying human hepatitis virus infection and human-liver specific drug response in mice with human livers.
- Mouse-human chimeras enable modeling stem cell replacement therapies to treat diseases such as diabetes or Parkinson’s.
- Chimeric mice with human neurons may identify treatments for devastating neural diseases, such as Alzheimer’s and Huntington’s diseases.
- Chimeras are routinely used in diagnostic tests, for example to test sperm fertility.
The ability to more accurately model human diseases in a system that can be studied in the lab help researchers uncover disease treatments that otherwise might not be found.
How Can Human-non-Human Chimeric Embryos Advance Human Health?
A chimeric embryo is created when pluripotent stem cells (i.e., cells that can become any cell in the body) are added to an embryo from the same or another species. These transplanted stem cells will generate new cells that will contribute to multiple tissues and organs in the growing organism.
Currently, researchers are able to transfer human cells into the embryos of other animals, such as mice, pigs, or non-human primates. Scientists are in the early stages of this chimeric embryo research, which has the potential to greatly enhance our understanding of human development and to generate better model systems for identifying new therapies. This research has the potential to improve the effectiveness of fertility treatment and to identify new ways of reducing birth defects and congenital diseases.
This emerging field of stem cell research may one day generate human tissues in animals for transplantation to humans. There are currently more than 100,000 adults and children on the transplant waiting list in the United States and more than 150,000 on the waitlist in Europe. Each day, at least 17 people in these regions die waiting for a transplant. Chimeric embryo research could lead to life saving transplant therapies in the future.
Studies using mouse-rat chimeras have demonstrated the feasibility of this approach to generate organs for transplantation. There are certain rat models that are unable to grow a pancreas. Mouse pluripotent stem cells transplanted into these rat embryos are able to generate the entire pancreas in these rats (Figure 1). Further proof of concept was demonstrated when cells from the rat pancreases could be transplanted back into mice with diabetes and reverse the disease.
In the future, human stem cells could be transplanted into the embryo of another animal and targeted to grow into specific organs, which could then be transplanted to a patient in need. Studies will reveal whether and how animal-human chimeras can be used to generate tissues for transplantation that would otherwise not be obtainable.
What is the Future of Chimeric Research?
To ensure that chimeric research is performed ethically, the International Society for Stem Cell Research’s (ISSCR) Guidelines for Stem Cell Research and Clinical Translation state that chimeric embryo research that involves human cells should be subject to review and approval by specialized research oversight committees. The guidelines call for research involving chimeric embryos to be done for the minimum time necessary to achieve the scientific aim, to proceed incrementally, and to limit widespread chimerism.
The current guidelines also prohibit certain research, including breeding chimeric animals that may have formed human eggs or sperm and transferring chimeric human-non-human embryos into the uterus of a human or certain non-human primates. To learn more about these guidelines see this commentary by the committee that crafted them, which explains and summarizes the recommendations.
The field holds significant potential for better understanding human development and creating new therapies. Chimeric research may uniquely identify new insights into human development, disease, and treatments that have the potential to help patients worldwide.