G.3 "Chimeras” in stem cell research
Chimera: An organism carrying cell populations derived from two or more (genetically distinct) sources, where the latter include zygotes, later stage embryos, liveborn animals, or cells grown in culture. N.B. While rare, some humans are natural chimeras due to the aggregation of two preimplantation stage embryos. More commonly, cells may cross the placental barrier from mother to fetus or vice versa and persist in the ‘host’ for life (Madam 2020). The word chimera should, therefore, be used as a neutral scientific term, in contrast to its mythological origins.
Interspecies chimeras: Interspecies chimeras are animals containing integrated cellular contributions from another species. The degree of contribution can range from minor to extensive. For example, chimeras can be derived when human stem cells are transferred into non-human embryos. There are three types of true human-animal chimeras bearing special concern: (a) those that have the capacity for widespread chimerism, and (b) those that have a significant degree of chimerism to the central nervous system and (c) those that have chimerism of the germline. Human-to-non-human primate chimeras or cellular xenotransplants formed at any stage of development warrant particular attention. For additional guidance on the review of human-animal chimeras, please consult the ISSCR white paper on chimeras (Hyun et al., 2020).
Cellular transplants into postnatal animal hosts:
Although formally the resulting animal can still be classed as chimera, where human cells with limited fate, in terms of cell type or tissue distribution are introduced into defined positions in postnatal animals (or late embryonic stages), this is usually referred to as a transplant or graft into a host. The graft can be homotopic, where it can integrate into the host tissue, or ectopic, where it may develop as a defined structure. Unless the methods involve transplanting human germ cells into animal gonads, these types of experiment will generally be of little concern, although they should be subject to review by an animal ethics committee.