Decreased immunogenicity of human fetal pancreas allografts following hyperbaric oxygen culture.
Human fetal pancreas (HFP) is a potential source of transplantable islets for the treatment of type 1 insulin-dependent diabetes mellitus (IDDM). Pretransplant culture techniques such as long-term culture, high-oxygen culture, UVB irradiation, and low-temperature culture have previously been used to reduce the immunogenicity of tissue for transplantation. In this study, we use hyperbaric oxygen culture (HOC) to modify MHC Class I expression on HFP and to reduce the immunological response of human peripheral blood mononuclear cells (PBMC) to HFP using a sponge matrix allograft model. To study the interaction of naïve PBMC with HOC-treated or untreated HFP allografts, sponges embedded with HFP tissue were implanted into the peritoneal cavity of NOD-SCID mice and injected with 1 x 10(7) freshly isolated human PBMC at the time of transplant. By day 14, human CD45 cells represented less than 2% of the cells recovered from the sponges implanted with HOC-treated HFP. In contrast, human CD45(+) cells represented nearly 15% (P =.0018) of the cells isolated from sponges implanted with conventionally cultured HFP grafts. Approximately 75% of the human CD45(+) cells from conventionally cultured HFP allografts were producing IFNgamma as determined by intracellular cytokine analysis. These data suggest that HOC treatment of HFP abrogates the activation and proliferation of PBMC. Pretransplant HOC treatment of islets is a simple technique that could be used to reduce immunogenicity and increase allograft survival while decreasing the requirement for immunosuppressive drugs.
MacKenzie
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DA
Department of Surgery, University of Wisconsin School of Medicine, Madison, Wisconsin 53792, USA. macken@surgery.wisc.edu
Sollinger
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HW
Hullett
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DA
D000818:Animals; D015703:Antigens, CD / Q000032:analysis; D003922:Diabetes Mellitus, Type 1 / Q000601:surgery; D004195:Disease Models, Animal; D016332:Fetal Tissue Transplantation / Q000276:immunology*; D006650:Histocompatibility Testing; D006801:Humans; D006931:Hyperbaric Oxygenation; D017493:Leukocyte Common Antigens / Q000032:analysis; D008285:Major Histocompatibility Complex; D051379:Mice; D016688:Mice, Inbred NOD; D009924:Organ Culture Techniques; D010179:Pancreas / Q000196:embryology; D016035:Pancreas Transplantation / Q000276:immunology*; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D014184:Transplantation, Homologous
D015703:Antigens, CD; D017493:Leukocyte Common Antigens; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1