The Large Animal Core will provide the facilities, management and technical expertise needed to supply miniature swine and baboons and tissue samples for all projects of the proposed program as well as expert veterinary care, immunological reagents, and microbiologic diagnostic assays and support. Clinical samples will be distributed to maximize utilization of each animal for studies of clinically relevant regimens for xenotransplantation. The success of each component of this program is dependent on the quality, predictability, and accessibility of the animals, microbiologic support, and antibodies provided by this Core. Animal care is reviewed weekly at meetings of the principal investigators and the veterinary staff.
The Aims of the Large Animal Core include:
Aim 1 : Purchase and maintenance of non-human primates;
Aim 2 : Production, quality control, tracking, and maintenance in an SPF facility of MGH MHC inbred miniature swine including the MGH GalT-KO swine, with homozygous disruption of the ?-1,3-galactosyltransferase gene (see Figures 1 and 2), and GalT-KO- CD47 transgenic swine. In the case of donors for Projects 1 and 2, these animals will be derived by Caesarian section into Hepa-filtered cages for assurance of pCMV-free maintenance until use;
Aim 3 : Develop and maintain new genetically modified swine in conjunction with Project 4;
Aim 4 : Provide diagnostic and management support related to infectious diseases, including prophylaxis and care paradigms for the care of immunosuppressed xenograft recipients and support of on-going studies by routine assessment of swine and baboon recipients for pCMV, bCMV, PERV and other pathogens;
Aim 5 : Provide diagnostic and management support related to vascular thrombosis, platelet sequestration and consumptive coagulopathy;
Aim 6 : Production and characterization murine monoclonal antibodies and swine antisera reactive with swine and baboon cell surface antigens. Animal care is a central component of this program and is reviewed weekly at laboratory meetings in which the principal investigators and veterinary staff participate.

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Research Program Projects (P01)
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Columbia University (N.Y.)
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Sykes, Megan (2018) IXA Honorary Member Lecture, 2017: The long and winding road to tolerance. Xenotransplantation 25:e12419
Proto, Jonathan D; Doran, Amanda C; Subramanian, Manikandan et al. (2018) Hypercholesterolemia induces T cell expansion in humanized immune mice. J Clin Invest 128:2370-2375
Chen, Mo; Wang, Yuantao; Wang, Hui et al. (2018) Elimination of donor CD47 protects against vascularized allograft rejection in mice. Xenotransplantation :e12459
Watanabe, Hironosuke; Sahara, Hisashi; Nomura, Shunichiro et al. (2018) GalT-KO pig lungs are highly susceptible to acute vascular rejection in baboons, which may be mitigated by transgenic expression of hCD47 on porcine blood vessels. Xenotransplantation 25:e12391
Sachs, David H (2018) Transplantation tolerance through mixed chimerism: From allo to xeno. Xenotransplantation 25:e12420
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Chen, Bing; Fan, Wei; Zou, Jun et al. (2017) Complement Depletion Improves Human Red Blood Cell Reconstitution in Immunodeficient Mice. Stem Cell Reports 9:1034-1042
Tena, Aseda A; Sachs, David H; Mallard, Christopher et al. (2017) Prolonged Survival of Pig Skin on Baboons After Administration of Pig Cells Expressing Human CD47. Transplantation 101:316-321

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