ALL STEM CELLS

Chimaeras are both monsters of the ancient imagination and a long-established research tool. Recent advances, particularly those dealing with the identification and generation of various kinds of stem cells, have broadened the repertoire and utility of mammalian interspecies chimaeras and carved out new paths towards understanding fundamental biology as well as potential clinical applications.

In Greek mythology, a chimaera is a fearsome fire-breathing beast composed of different parts of more than one animal, vividly depicted in Homer’s Iliad as a lion-headed creature with the body of a goat and the tail of a serpent. In modern bioscience, chimaeras are entities made up of cells from different organisms. They are extremely valuable basic biology research tools with the potential for future clinical use. Experimental chimaeras generated from cells of more than one individual of the same species, particularly the mouse, have been widely used for many biomedical studies. Here, however, we focus on mammalian chimaeras generated
from different species, also known as interspecies chimaeras*, which have recently garnered attention among researchers and the public, owing to their potential for providing replacement human organs.
This Review will first provide a historical perspective and a summary of recent advances in stem-cell-derived interspecies chimaeras and their potential applications. It will go on to discuss ethical guidelines, current policies, societal effects and, finally, conclude with an outlook on research in this and related areas. Interspecies chimaera-related research covers a broad range of topics. We focus here on studies that deliver donor stem cells to pre-natal host embryos and fetuses—research on conventional xenotransplantation approaches involving the introduction of donor cells into the post-natal animal has been reviewed elsewhere.

SEE MORE : NATURE 2016 DECEMBER

Defining chimaeras
A chimaera is typically defined as an organism composed of a mixture of different cell populations that derive from more than one zygote.
They can be formed by processes such as the mixing of early embryos or the grafting of tissues from different stages of development or the adult. Chimaeras are distinct from hybrids (offspring resulting from breeding between different species) and from mosaics (animals carrying genetically different cells that originated from the same zygote).
Chimaeras can be categorized as intraspecies or interspecies, depending on whether cell derivatives from two zygotes are from the same or different species, respectively.
Creating interspecies chimaeras requires a donor species and a host species. The donor species provides cells of embryonic, fetal, or adult origin, either from primary tissue or from cell cultures. The host species provides the physiological environment and life support for embryonic, fetal, or adult chimaeric animals. In stem-cell research, the generation of an interspecies chimaera often involves the transplantation of multi- or pluripotent stem (PS) cells from the donor into an animal recipient at embryonic, fetal or post-natal stages of development.
Tissue distribution and duration of chimaerism often differ depending on the donor cell type and the developmental stage of the host. PS cells are less restricted in developmental potential than other stem-cell types and thus can give rise to a high degree of chimaerism with wide tissue distribution when transferred to pre-implantation host embryos. Chimaeras generated by progenitors or adult stem cells are more confined to specific tissues and may need to be grafted to appropriate sites and developmental stages. Chimaeras are often designated according to the developmental age of the host at the time of analysis (for example, chimaeric embryos and chimaeric fetuses) or at the time of donor cell injection (for example, blastocyst chimaeras).
Other important distinctions are between heterotopic and orthotopic, and heterochronic and isochronic chimaeras. Orthotopic chimaeras are generated by transplanting donor cells to their cognate location where they can participate in natural developmental processes or proper tissue
organization of the host (for example, transplanting donor hepatocytes to the host liver). Heterotopic chimaeras occur with differentiation or integration of donor cells at a different site within the host animal than their origin (for example, transplanting donor pancreatic β -cells to the host
liver). Heterochronic and isochronic chimaeras are distinguished by the temporal properties between donor and host. If donor cells are delivered to the host at a time matching their in vivo origin, an isochronic chimaera will be formed, otherwise the chimaera formed will be heterochronic.