Xenotransplantation and interspecies organogenesis: current status and issues

Abstract

Pancreas (and islet) transplantation is the only curative treatment for type 1 diabetes patients whose β-cell functions have been abolished. However, the lack of donor organs has been the major hurdle to save a large number of patients. Therefore, transplantation of animal organs is expected to be an alternative method to solve the serious shortage of donor organs. More recently, a method to generate organs from pluripotent stem cells inside the body of other species has been developed. This interspecies organ generation using blastocyst complementation (BC) is expected to be the next-generation regenerative medicine. Here, we describe the recent advances and future prospects for these two approaches.

Keywords: blastocyst complementation; chimera; islet; pancreas; pluripotent stem cells; type 1 diabetes; xenotransplantation.

Figure 1

Differences between xenotransplantation and animal-developed human organ transplantation by using blastocyst complementation. In xenotransplantation (top), a small percentage of the xenografts have proteins derived from the human transgene, but the majority are of porcine origin. On the other hand, the blastocyst complementation (bottom) generates organs almost completely of human origin in a specific organ-deficient animal. Cartoon pictures (human transgene, pig, and human) were created with BioRender.

Figure 2

Blastocyst complementation using organ-deficient mice. Blastocyst complementation using Pdx1 ^−/− pancreas-deficient mice. When wild-type pluripotent stem cells (PSCs) are injected into blastocysts derived from a genetically pancreas-deficient mouse, the injected PSCs can complement an empty developmental niche for a pancreas. Whereas the skin, tissues, and organs throughout the body of the chimeric mouse are composed of a mixture of PSCs and host embryos, the pancreas is composed entirely of cells derived from the donor PSCs. The lower right is a photograph of an interspecific chimera. This Pdx1 ^−/− mouse complemented with rat PSCs has a pancreas derived from rat PSCs.