The frontiers of xenotransplantation have been further extended with a pig-to-human lung transplant, the first time an organ that is directly exposed to the external environment – with the associated risk of respiratory pathogens – has been transplanted. The genetically modified pig lung remained viable and functional for nine days, after it was transplanted into a 39-year-old man who was declared brain dead following a hemorrhagic stroke.

Eledon Pharmaceuticals Inc.’s tegoprubart, an investigational anti-CD40 ligand antibody, was used as part of the immunosuppressive regimen after the first-ever transplant of a kidney from a genetically modified pig to a human. The tegoprubart procedure was done March 16 at Massachusetts General Hospital on a 62-year-old man with end-stage renal disease.

Scientists at the University of California San Francisco (UCSF) have designed a group of synthetic molecules that could prevent the rejection of allogeneic cell transplants. Their strategy consisted of activating the immune checkpoints of different populations of immune cells from the cell surface, but avoiding the cytotoxicity of natural killer (NK) cells and macrophages that would destroy the transplanted cells.

Scientists at Egenesis Inc. have transplanted kidneys from genome-edited pigs into cynomolgus monkeys that remained functional for long periods after transplantation. The monkeys, whose own kidneys were removed during the surgery, survived for a median of 176 days after receiving one pig kidney. Maximal survival was just over 2 years. The data were published today in Nature. Egenesis CEO Mike Curtis told reporters that the study has achieved the longest survival to date “using clinically translatable immunosuppression … longer survival has been achieved using really aggressive immunosuppression that really isn’t clinically translatable.”

Scientists at Egenesis Inc. have transplanted kidneys from genome-edited pigs into cynomolgus monkeys that remained functional for long periods after transplantation. The monkeys, whose own kidneys were removed during the surgery, survived for a median of 176 days after receiving one pig kidney. Maximal survival was just over 2 years. The data were published today in Nature. Egenesis CEO Mike Curtis told reporters that the study has achieved the longest survival to date “using clinically translatable immunosuppression … longer survival has been achieved using really aggressive immunosuppression that really isn’t clinically translatable.”

Scientists at the Guangzhou Institutes of Biomedicine and Health have developed a humanized kidney at the mesonephros stage in pig embryos up to day 28 of gestation. It is the first time that this has been achieved in chimeric xenotransplants.

Gene therapy technology makes it possible to select diseased or mutated cells from a patient, modify them in the laboratory and reintroduce them to the body to treat different disorders. This is known as ex vivo autologous gene therapy. The difference with allogeneic cell techniques is whether the donor is oneself (autologous) or a compatible person (allogeneic), which would provide healthy cells that do not need genetic modification.

The limited state of current clinical transplantation science was recently the subject of an opinion piece from an individual that received her first heart transplant at just 25 years of age only to soon succumb at the age of 60 to one of the many risky outcomes expected for anyone taking standard requisite immunosuppression regimens used for any transplantation, in her case terminal cancer.

Base editing (BE), a technique that modifies a single nucleotide in living cells, has been successfully tested to resolve the CD3δ mutation in severe combined immunodeficiencies (SCIDs) and produce functional T cells. For now, scientists at the University of California, Los Angeles (UCLA), completed the study on patient stem cells and artificial thymic organoids, shortening the way for future clinical trials.