Concept of Chimeric Organisms Such as Human/Non-Human Chimera (HNH-Chimera)

As an another direction in the xenotransplantation, chimeric organisms are recently represented in the regenerative medicine using the stem cells (SCs). For definition of chimeric transplantable compatibility, human organs can be generated from pigs usable for xenotransplantation because of the non-new concept of chimeric animals. Since the embryonic chimera from goat and sheep embryos was firstly created in 1984, at present, the ethical issue of the human-derived gamete and animal gamete fertilization is raised with the moral acceptance of human/non-human chimera (HNH-chimera) [1]. In pigs, such chimera is needed to develop animals, which have human organs. In addition, pigs and humans have similar metabolism, physiology, long habitation with human population, and sizes of organs. In addition, the administration of pig cells to humans’ xenotransplantation is beneficial for identification of the infectious and immunological risks and barriers [2]. In the chimeric model of rodents, pluripotent stem cell (PSC) injection of rats is made to mice blastocysts as rat-mouse chimeras and the chimera developed into adulthood. Those chimeras can efficiently be constructed by the CRISPR-Cas9 genome editing, as the rodent chimera organs with rat cells can be created [3]. When chimeric competency of human PSCs (hPSCs) was examined in cattle and pigs, the integration has stably been progressed by intermediate hPSCs to the pig embryo progenitors [3]. This inter-species of human–pig blastocyst complementation is in progress.