Researchers from the University of Missouri have successfully developed a line of genetically engineered pigs that hosted transplanted human induced pluripotent stem cells (iPSCs) without rejecting them. These pigs could therefore serve as a valuable tool for investigating the safety and regenerative capacity of iPSC tissue grafts. The study has been published in Proceedings of the National Academy of Sciences of the United States of America.
“The rejection of transplants and grafts by host bodies is a huge hurdle for medical researchers,” said Michael Roberts, co-author of the study and Curators Professor of Animal Science and Biochemistry. “By establishing these pigs will support transplants without the fear of rejection can move stem cell therapy forward at a quicker pace.”
Stem cell research has come on leaps and bounds over the last few years and it is believed that these cells could be a valuable tool for regenerative medicine, especially in personalized tissue transplantation. However, there exists some uncertainty about the safety of stem cells, in particular iPSCs, and whether these cells are truly able to differentiate into any type of cell (are fully pluripotent). Furthermore, much research has relied on the use of rodent models which are limited since they are inappropriate for simulating certain human genetic and infectious diseases, and their physiology is significantly different from that of humans.
Pigs, on the other hand, can mimic various human diseases more closely than rodents and our physiologies and immune cell populations are also much more similar. These animals are therefore more attractive models, especially in the field of regenerative medicine. According to Randall Prather, one of the lead researchers of this study, the similarities between pigs and humans means that research in these animals is more likely to yield results that are akin to those in humans.
For this study, researchers genetically modified pigs so that they presented a severe combined immunodeficiency (SCID) phenotype. These SCID pigs did not produce antibodies and lacked both B and T cells, which are major players in the adaptive immune response. After implanting human iPSCs into these pigs they found that the cells were not rejected and they went on to form a wide range of tissues.
Since these pigs are immune compromised, they need to be kept in clean environments to prevent infection which could easily lead to death. However, the researchers conclude that provided this can be done, these pigs could be an invaluable tool to test the safety and regenerative capacity of human stem cells and also as models for human patients with equivalent immunodeficiencies.
“Now that we know that human stem cells can thrive in these pigs, a door has been opened for new and exciting research by scientists around the world,” said Roberts in a news-release. “Hopefully this means that we are one step closer to therapies and treatments for a number of debilitating human diseases.”
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