A Longer Road for Xenotransplantation of Pig Hearts into Humans
A great deal of time and effort was required to achieve the first pig to human heart transplant, including the production of genetically engineered pigs that lack the cell features that provoke rejection, and which minimize the presence of porcine viruses. Nonetheless, the first transplanted heart failed after some weeks for reasons that are yet to be determined, undergoing widespread cell death. This suggests that the remainder of the path towards viable xenotransplantation will be longer than hoped. As a strategy, xenotransplantation competes with work on the production of organs built from patient cells, an approach that will likely take at least as long to be realized.
The pig that served as the heart donor came from a population that has been extensively genetically engineered to limit the possibility of rejection by the human immune system. The line was also free of a specific virus that inserts itself into the pig genome (porcine endogenous retrovirus C, or PERV-C) and was raised in conditions that should limit pathogen exposure. The animal was also screened for viruses prior to the transplant, and the patient was screened for pig pathogens afterward.
While patient weight loss was a concern, at five weeks after the transplant, there were no indications of rejection, and the heart was still functioning. Things started to go bad about seven weeks post-transplant when the patient's blood pressure began to drop. Fluid started building on his lungs, and he had to be intubated. Imaging showed that his heart was still clearing out most of the volume of the ventricles with each beat, but the total volume had shrunk as the walls of the ventricle thickened. Eventually, external oxygenation had to be restarted.
Pig DNA began to show up in the bloodstream, indicating tissue damage; some anti-pig-cell antibodies were also detected, suggesting a degree of rejection. But a biopsy failed to find any signs of it in the heart tissue; instead, there were signs that capillaries in the heart were leaking, creating swelling and allowing blood cells into the heart tissue. A week later, a second biopsy indicated that about 40 percent of the heart muscle cells in the transplant were dead or dying, even though there were still no indications of rejection in the tissue. That level of damage brought an end to things and life support was withdrawn.
Link: https://arstechnica.com/science/2022/06/pig-heart-transplant-failed-as-its-heart-muscle-cells-died/
This was unfortunate. I had a heart transplant 15yo and it may not last many years. Biolife4d is soon going to have IPO. eGenesis is interesting to follow in the xenotransplantation space.
It is indeed unfotunate development. However, it was really surprising that it worked in the first place. I was expecting many more years of cautious experiments with a tissue patches here and there . Now we will have to go back to a series studies where the pig tissue is implanted to living humans in non-critical or functional part of the body to see what factors caused such "toxicity". I guess part of the problem is that many rejection studies were done for relatively short periods of time. Like a month. And here for the first month everything was going just fine. And here it seems more like a graft vs host issue.
Is a new heart a step too far for Lygenesis? Having said that they have some very important but lofty goals on their agenda already.