SCID pigs: An emerging large animal NK model

Abstract

Severe Combined ImmunoDeficiency (SCID) is defined as the lack or impairment of an adaptive immune system. Although SCID phenotypes are characteristically absent of T and B cells, many such SCID cellular profiles include the presence of NK cells. In human SCID patients, functional NK cells may impact the engraftment success of life saving procedures such as bone marrow transplantation. However, in animal models, a T cell-, B cell-, NK cell+ environment provides a valuable tool for asking specific questions about the extent of the innate immune system function as well as emerging NK targeted therapies against cancer. Physiologically and immunologically the pig is more similar to the human than common rodent research animals. This review discusses why the T-B-NK+ SCID pig may offer a more relevant model for development of human SCID patient therapies as well as provide an opportunity for systematic exploration of the role of NK cells in artiodactyl immunity.

Severe combined immunodeficiency pig as an emerging animal model for human diseases and regenerative medicines

“…The advantage of the pig model is its similarity to humans in genetic makeup, anatomy, and physiology. Previous studies have demonstrated that analyzed parameters of pig immune system are 80% similar to human, while there is only a 10% similarity between human and mouse (2, 80, 81). The SCID mouse is widely used because of the generation of the humanized model in which HSCs cells are induced to a given SCID host to permit the differentiation of elements involved in the immune system (82).…”

“…Researchers have tried to extend the applicability of the pig model due to similarity of pig’s immune system to human. Several SCID pig models have already been generated (2, 83). A humanized pig disease model as a research platform will be a breakthrough that can transform preclinical research because it is the closest animal model to human.…”

“…A naturally occurring SCID in humans was first described in the 1960s. It was subsequently acknowledged in horses, mice, dogs, and recently in pigs (1, 2). SCID was thought to be inherited from a recessive gene linked to either X-chromosome or an autosome.…”

Cellular Therapies for the Treatment of Hematological Malignancies; Swine Are an Ideal Preclinical Model

“…The recent development of the SCID pig provides an interesting avenue for studying the role of NK cells in both allogeneic and xenogeneic anti-tumor responses in a large animal model (67). Similarly to human NK cells, swine NK cells can be identified by expression of CD3 − CD16 + CD56 + surface markers (68).…”