A new type of stem cell could open the door to humanized pig parts for transplantation into human recipients
Organ donation often requires someone else's death, under circumstances that facilitate viable organ harvest. Living donors also make a life-altering impact for patients who can benefit from a kidney or parts of tissues that can be spared. However, making donor and recipient connections is a long shot that necessitates screening for tissue match, blood type, and immune status, among other constraints.
It is apparent that the dependence on human donors is not a viable option, for there are about five times more patients on the waiting lists than can be successfully matched. Xenotransplantation, or transplantation of animal parts into humans, is an alternative that was attempted in the 1960s but not pursued for its limited success. With recent advances in science, could we revisit xenotransplantation?
A group of scientists recently published the discovery of a new type of stem cell, designated as region-selective pluripotent stem cells, or rsPSC. The intriguing characteristic displayed by rsPSC was its ability to effectively generate chimeric embryos (hybrids of two individuals). But more importantly, it did not matter whether the rsPSC and recipient embryo were from the same species or different species.
To begin their project, scientists developed cell culture conditions to expand cells taken from the epiblast stage of development of the donor mouse embryo. Parameters to arrest cell growth in a continuous proliferative state were adopted. The mouse rsPSCs obtained in this manner were able to graft the posterior region of recipient mouse epiblasts.
Scientists also derived human and non-human primate rsPSCs and once again succeeded at grafting mouse embryo epiblasts. In contrast, human embryonic stem cells (ESCs) did not have the capacity to graft mouse post-implantation epiblasts, thereby highlighting one of the limitations of ESCs. The discovery of rsPSCs therefore opens up a novel platform for generating inter-species chimeras, using stem cells and recipient embryos from two different species.
While pigs have been explored for donor tissue, the human immune system has antibodies to a sugar molecule called alpha-1,3-galactose (a-gal), present in pigs. To date, pigs have been engineered without the a-1,3-galactosyltransferase gene responsible for the a-gal protein, but with human cell membrane proteins (CD55 and CD46) to enhance acceptance of pig cells by the human immune system.
It just may be possible one day to use the new stem cells to create human-pig chimeras in genetically engineered pigs that enable the use of humanized tissues and organs. At HemaCare, we provide stem cells for research and are intrigued by implications for life-saving medicine.
- Wu J, et al. An alternative pluripotent state confers interspecies chimaeric competency. Nature. 2015 May 6.
- Ekser B, et al. Comparison of hematologic, biochemical, and coagulation parameters in α1,3-galactosyltransferase gene-knockout pigs, wild-type pigs, and four primate species. Xenotransplantation. 2012 Nov-Dec;19(6):342-54