The Islet Isolation and Transplantation Core will provide Project investigators with a reliable supply of isolated mouse, rat, and human pancreatic islets for use in transplantation. Mouse and rat islets will be prepared by the personnel of the Core. Human islets will be obtained from Dr. Camillo Ricordi at the University of Miami. The Islet Core will supervise the receipt, assessment, counting, and distribution of the human islets. Core personnel will also perform all islet transplantation surgery. The need for this Core was recognized in our previous proposal, and our laboratory has supported the activities of an Islet Isolation Core since 1991. The need for the core is determined by both biological and logistical considerations. Islets comprise less than 1% of the mass of the pancreas, are distributed nearly uniformly throughout a gland laden with digestive enzymes, and are fixed in position by a network of vasculature and fibrous tissue. Their isolation is a time-consuming procedure that requires considerable skill. On average, each mouse or rat islet transplant recipient requires all the islets that can be obtained from about four donors. In our experience, one technician can process enough donors to transplant 3 to 4 chemically diabetic mice per day. Each mouse requires 20 islets per gram of body weight to restore normoglycemia. Program Project investigators anticipate performing 1,500 to 2,000 transplants yearly, all using mouse recipients. One technician engaged in islet isolation will be required to satisfy the projected need for mouse and rat tissue and to transplant all mouse, rat, and human islets. The procedures required for islet transplantation beneath the kidney capsule require the development and maintenance of surgical skill. The level of skill required is particularly high because of the need to maintain strict asepsis; many of the transplants will be performed using immunodeficient scid mice. The proposed Islet Isolation Core facility is intended to avoid duplication of effort in the Program Project's laboratories and enhance quality control. The Core will also facilitate the Program Project concept by standardizing a key shared methodology, allowing comparisons of results among Projects. Our islet isolation procedure is a modified collagenase method carried out under aseptic conditions. If investigators should require additional processing of islets in the form of prolonged culture to remove passenger leukocytes or the preparation of porcine islets, the Islet Core can also provide this service. Islet transplantation will be performed by the Core staff in viral antibody free quarters in the case of rat recipients and in a special quarantine facility in the case of scid mice.

Project Start
1997-09-30
Project End
1998-11-30
Budget Start
1997-10-01
Budget End
1998-09-30
Support Year
1
Fiscal Year
1998
Total Cost
Indirect Cost
Name
University of Massachusetts Medical School Worcester
Department
Type
DUNS #
660735098
City
Worcester
State
MA
Country
United States
Zip Code
01655
Covassin, L; Laning, J; Abdi, R et al. (2011) Human peripheral blood CD4 T cell-engrafted non-obese diabetic-scid IL2r?(null) H2-Ab1 (tm1Gru) Tg (human leucocyte antigen D-related 4) mice: a mouse model of human allogeneic graft-versus-host disease. Clin Exp Immunol 166:269-80
Brehm, Michael A; Shultz, Leonard D; Greiner, Dale L (2010) Humanized mouse models to study human diseases. Curr Opin Endocrinol Diabetes Obes 17:120-5
Racki, Waldemar J; Covassin, Laurence; Brehm, Michael et al. (2010) NOD-scid IL2rgamma(null) mouse model of human skin transplantation and allograft rejection. Transplantation 89:527-36
Brehm, Michael A; Cuthbert, Amy; Yang, Chaoxing et al. (2010) Parameters for establishing humanized mouse models to study human immunity: analysis of human hematopoietic stem cell engraftment in three immunodeficient strains of mice bearing the IL2rgamma(null) mutation. Clin Immunol 135:84-98
de Vries, V C; Elgueta, R; Lee, D M et al. (2010) Mast cell protease 6 is required for allograft tolerance. Transplant Proc 42:2759-62
Brehm, Michael A; Bortell, Rita; Diiorio, Philip et al. (2010) Human immune system development and rejection of human islet allografts in spontaneously diabetic NOD-Rag1null IL2rgammanull Ins2Akita mice. Diabetes 59:2265-70
Jurczyk, Agata; Pino, Steven C; O'Sullivan-Murphy, Bryan et al. (2010) A novel role for the centrosomal protein, pericentrin, in regulation of insulin secretory vesicle docking in mouse pancreatic beta-cells. PLoS One 5:e11812
Mangada, Julie; Pearson, Todd; Brehm, Michael A et al. (2009) Idd loci synergize to prolong islet allograft survival induced by costimulation blockade in NOD mice. Diabetes 58:165-73
King, M A; Covassin, L; Brehm, M A et al. (2009) Human peripheral blood leucocyte non-obese diabetic-severe combined immunodeficiency interleukin-2 receptor gamma chain gene mouse model of xenogeneic graft-versus-host-like disease and the role of host major histocompatibility complex. Clin Exp Immunol 157:104-18
King, Marie; Pearson, Todd; Shultz, Leonard D et al. (2008) A new Hu-PBL model for the study of human islet alloreactivity based on NOD-scid mice bearing a targeted mutation in the IL-2 receptor gamma chain gene. Clin Immunol 126:303-14

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