The organ shortage is severe enough that the domestic pig is being taken seriously as a source. Animal models had established safety and feasibility, but an animal is not a person, and no clinical trial can start on the strength of one. Porrett and colleagues needed a human test with no patient at risk. What did they do?
They worked in a brain-dead decedent. After a novel prospective compatible , the team removed both native kidneys and transplanted two kidneys from a pig genetically engineered for human . The decedent stayed hemodynamically stable through reperfusion, vascular integrity held under human blood pressure, no appeared, and the kidneys stayed viable until the study ended.
The authors open with the problem rather than the technique: a radical solution is needed for the organ supply crisis, and the domestic pig is a promising organ source. Safety and feasibility tenets had been established in animal models. What was missing was a way to test them in a human being without exposing a patient to the risk.
Their model is a brain-dead decedent. After a novel, prospective compatible crossmatch, the team removed both native kidneys. They then transplanted two kidneys from a pig genetically engineered for human xenotransplantation, so the only kidneys in the body were the porcine ones.
The immediate results were favorable. The decedent remained hemodynamically stable through reperfusion. Vascular integrity was maintained despite exposure of the xenografts to human blood pressure. No hyperacute rejection appeared, and the kidneys remained viable until termination seventy-four hours later. No chimerism was found, and no transmission of porcine retroviruses.
The qualifications are as specific. Longitudinal biopsies revealed , which did not progress in severity, with no cellular rejection and no deposition of antibody or complement proteins. The xenografts produced variable amounts of urine, but creatinine clearance did not recover. The authors say outright that whether renal recovery was affected by the milieu of brain death, by microvascular injury, or by something else remains unknown. Their summary is that major barriers appear surmounted and that this is where new knowledge is needed.
wat. Two pig kidneys in a human body for three days: no hyperacute rejection, no retrovirus, and no working clearance either.
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It is a way to put a xenograft inside a human circulation, under human blood pressure, with nobody who could be harmed by the answer.
How do we know?
An American Journal of Transplantation report of an in vivo pre-clinical human model: bilateral native nephrectomies and bilateral porcine kidney transplant in a brain-dead decedent, with longitudinal biopsies and screening for chimerism and porcine retroviruses.
What is still unknown
Function did not return. The grafts made variable amounts of urine but creatinine clearance did not recover, and whether that reflects brain death, microvascular injury or the xenograft itself is unknown.
Learn something?
Where to next
How do you treat a disease by switching a different gene back on?gene editing