Xenogeneic chimera—Generated by blastocyst complementation—As a potential unlimited source of recipient‐tailored organs

Abstract

Blastocyst complementation refers to the injection of cells into a blastocyst. The technology allows for the creation of chimeric animals, which have the potential to be used as an unlimited source of organ donors. Pluripotent stem cells could be generated from a patient in need of a transplantation and injected into a large animal blastocyst (potentially of a pig), leading to the creation of organ(s) allowing immunosuppression-free transplantation. Various chimera combinations have already been generated, but one of the most recent steps leads to the creation of human-pig chimeras, which could be studied at an embryo stage. Although still far from clinical reality, the potential application is almost unlimited. The present review illustrates the historical steps of intra- and interspecific blastocyst complementation in rodents and large animals, specifically looking at its potential for generation of organ grafts. We also speculate on how it could change transplant indications, on its economic impact, and on the linked ethical concerns.

Xenotransplantation: back to the future?

“…Intraspecies (autologous) or interspecies (xenogeneic) organ‐specific chimeric embryos can be generated only in the presence of a “developmental niche” . Therefore, organ‐specific developmental genes need to be removed or repressed for the pluripotent cells to restore the defect and normal organ development, a process named blastocyst complementation .…”

Ethical rejections of xenotransplantation?

“…There are at least four specific challenges that need to be resolved before this can become a reliable source of human organs [1]. So far, pigs have been the most common source of organs as they hold several advantages for xenotransplantation: the similar size of pig organs to human organs; the ease with which it is possible to clone and genetically modify pigs; the large number of progeny; and the fact that pigs have a relatively short reproduction time and require only about 6 months to grow a sufficiently large and transplantable organ.…”

“…Basically, it would involve seeding a pig blastocyst or embryo with human stem cells that would eventually grow into the desired organ. There are at least four specific challenges that need to be resolved before this can become a reliable source of human organs [1]. First, master gene regulators of organ development in pigs need to be identified to prevent the development of the organ that is to be grown from the human cells.…”

Xenotransplantation literature update, July/August 2017

“…Oldani and colleagues reviewed the historical progress of blastocyte complementation and discussed the potential challenges, technological aspects, economic implications, and ethical limitations of the generation of human‐pig chimera using this technology . Initially, successful usage of pluripotent stem cells (iPSCs) for organ complementation in rodents with gene deletions, and the successful generation of chimeric mice using rat iPSCs and vice versa, validated the feasibility of this technology, across species barriers (at least in the concordant xenogeneic combination).…”