Open Review Describes Three Routes for Growing Human Cells and Organs in Animals
Open Review Describes Three Routes for Growing Human Cells and Organs in Animals
On August 24, an open-access review of animal bioreactors was published. The authors grouped the approaches by their intended product: a complete organ, cells directed into a specific tissue, or an expanded cell product.
An animal bioreactor uses the embryo's developmental program. In blastocyst complementation, a gene required for the development of a particular organ is disabled in the host embryo. Donor pluripotent cells, which can develop into multiple tissue types, occupy the vacant niche and develop alongside the host.
This principle worked in a 2010 experiment. Researchers disabled a gene required for pancreatic development in a mouse embryo. The introduced rat cells occupied the resulting niche and formed a functional rat pancreas. This interspecies experiment showed that a vacant niche can direct donor cells to form an entire organ.
An organ consists of several interconnected tissues. The endothelium, which lines the inside of blood vessels, is especially important because vessels of mixed origin may trigger immune rejection. In a 2020 study, researchers disabled ETV2, a gene required for vascular and hematopoietic lineages, in pig embryos and introduced human induced pluripotent cells. On day 17–18, all detected endothelial cells were of human origin. This experiment tested whether a niche could also be created for the vascular component of a future organ.
In a 2023 study, human cells were introduced into pig embryos with impaired development of the kidney lineage. By day 28, the embryos had formed organized mesonephros structures, which are temporary embryonic kidney structures, containing human cells. This experiment tested whether the cells could integrate into an organized kidney niche rather than merely persist as isolated cells.
The review distinguishes three engineering routes. Blastocyst complementation begins at the earliest embryonic stage and aims to assemble an organ. A local organogenic niche introduces progenitor cells later, while the organ is forming. The third route uses a postnatal animal with a deliberately weakened immune system to expand liver or blood cells.
The intended product therefore determines the bioreactor design. To produce blood cells, the animal must generate large numbers of individual cells. Producing a kidney, heart, or liver requires the coordinated growth of tissues, blood vessels, and nerves. The intended product determines the niche, the type of donor cells, and the organ components that must develop together.