Old World Monkeys are Less than Ideal Transplantation Models for Testing Pig Organs Lacking Three Carbohydrate Antigens (Triple-Knockout)

Pooled Human Serum Off The Clot from Innovative Research was used in the following study:

Old World Monkeys are Less than Ideal Transplantation Models for Testing Pig Organs Lacking Three Carbohydrate Antigens (Triple-Knockout)

Takayuki Yamamoto, Hayato Iwase, Diyan Patel, Abhijit Jagdale, David Ayares, Douglas Anderson, Devin E. Eckhoff, David K. C. Cooper & Hidetaka Hara

Scientific Reports
June 17, 2020

Choosing the best nonhuman primate (NHP) model to perform pig-to-NHP xenotransplantation is crucial to determine the feasibility of pig organ transplantation in humans. Triple-knockout (TKO) pigs (with added protective human transgenes) are likely to be optimal sources of organs for clinical organ xenotransplantation because many humans have minimal or no natural antibody to TKO pig cells. Old World monkeys (OWMs), such as baboons or rhesus monkeys, have been used as the preferred species for preclinical studies of pig kidney xenotransplantation. However, OWMs have naturally-existing antibodies directed to TKO cells.

The aim of the study was to investigate (i) anti-pig IgM/IgG binding, and (ii) serum CDC to wild-type (WT), GTKO, and TKO pig peripheral blood mononuclear cells (PBMCs), and (iii) to compare the survival of GTKO (with added human transgenes) pig kidneys with that of TKO (with added transgenes) pig kidneys in baboons using an anti-CD40mAb-based immunosuppressive regimen. Cytotoxicity of OWM sera to TKO PBMCs was significantly greater than of human serum, but there was no significant difference between human and NWM sera. The median survival of TKO pig kidneys (4 days) in baboons was significantly shorter than that of GTKO kidneys (136 days) (p < 0.05). Even though considered ideal for clinical xenotransplantation, the presence of naturally-existing antibodies to TKO pig cells in OWMs complicates the transplantation of TKO pig kidneys in OWMs. While most OWMs have naturally-existing antibodies against TKO pig red blood cells (pRBCs), many capuchin monkeys (a new World Monkey [NWM]) do not have such antibodies, or have antibodies at low levels, and thus more closely mimic humans with respect to the response to TKO cells.

Related products available from Innovative Research also include:

Pooled Human Complement Serum

Pooled Human Plasma (Blood Derived)

Single Donor Human Serum Off The Clot