What are Xenograft models? Use of Immunocompromised Rodents in Cancer Research and Oncology Drug Development 

The term xenograft refers to a transplant of an organ or tissue from a donor that comes from a different species than the recipient. It is possible to engraft human and other species’ cells and tissues into immune-deficient models, especially from cancer cells. 

Cancer research relies heavily on xenografts. An immunodeficient or humanized mouse can be transplanted with a small segment of a cancer patient’s tumor to develop a personalized treatment plan. They are known as patient-derived xenografts (PDX). 

Xenograft models allow for the study of the tumor’s growth patterns, behavior, and personalized treatment. Depending on its location, it can be transplanted under the skin or into the organ from which the tumor originated. 

The history of xenograft models

The xenotransplantation procedure – from the Greek for “foreign” – involves transplanting living cells, tissues, or organs from one species to another. These exogenous cells, tissues, or organs are called xenografts or xenotransplants. It differs from allotransplantation (from one individual of the same species), syngeneic transplantation (grafts transplanted between two genetically identical individuals), and autotransplantation (from one part of the body to another within the same individual). 

In preclinical oncology research, human tumor cells are often transplanted into immunocompromised mice. End-stage organ failure is a significant health problem in developed nations, and human Xenotransplantation offers a potential cure. But it raises several new medical, legal, and ethical issues. It is a continuing concern that many animals, such as pigs, live shorter lives than humans, causing their tissues to age faster.  

It is also important to be concerned about diseases transmitted by animals (xenozoonosis) and permanent changes to their genetic code. The ethical objections to Xenotransplantation are similar to those raised against animal testing. Although, Several cases of Xenotransplantation are reported to be temporarily successful. 

While patients and physicians usually use the term “allograft” imprecisely to refer to both allografts (human-to-human) and xenografts (animal-to-human), maintaining the more precise distinction is helpful scientifically (for those searching or reading scientific literature). 

The first xenograft attempt

Scientific literature first attempted Xenotransplantation (then heterotransplantation) in 1905, when rabbit kidney slices were transplanted into a child with chronic kidney disease. Several subsequent studies used lambs, pigs, and primates’ organs in the first two decades of the 20th century. 

After the immunological basis of organ rejection, scientific interest in Xenotransplantation declined. As immunosuppressive drugs were discovered, subsequent waves of research emerged. After Joseph Murray’s first successful kidney transplant in 1954, scientists looked for alternatives to human organs for the first time.