PANCREATIC TRANSPLANTATION AND DIABETES MELLITUS

Project: Research project

Description

Further refinements in the technique we currently use to isolate
human islets are proposed. The procedure will test several
solutions constructed to stabilize cells during collagenase
digestion, and will introduce a hydroclone device to facilitate
bulk separation of liquid from solids in the final digestion
slurp. We will continue to modify a special centrifuge that will
have capacity sufficiently large to hold the total digestion slurp
in a discontinuous gradient composed of Eurocollins-Ficoll and/or
Eurocollins-Albumin. The-gradient will be emptied by activating a
hydraulic system that permits the key gradient layers to be
harvested directly into a sterile plastic bag that is used to
infuse the islet preparations. Clinical transplantation trials,
already initiated, will be expanded and the effects on islet
allograft survival of several different immunosuppression regimens
will be compared. We will also generate a series of canine
monoclonal antibodies directed against canine dendritic cells and
'macrophages, as well as to T cell subsets. CD4 and CD8 peptides
will be synthesized based on sequence analysis data obtained from
cloned cDNAs which encode these canine lymphocyte antigens. The
peptides will be used to generate anti-CD4 and anti-CD8 MoAbs.
The anti-dendritic cell and anti-macrophage MoAbs will be used to
immunomodulate canine islets, in vitro. The anti-CD4 and anti-CD8
MoAbs will be used for recipient immunotherapy, alone, in
combinations, and in association with low dose cyclosporine or
FK506. Dogs with pancreatectomy-induced diabetes will be used to
evaluate the potential value of deletion of CD4 and/or CD8 T cells
in vivo for immunosuppression and/or tolerization to islet
allografts.
StatusFinished
Effective start/end date5/1/804/30/07

Funding

  • National Institutes of Health
  • National Institutes of Health: $659,589.00
  • National Institutes of Health: $642,177.00
  • National Institutes of Health: $608,862.00
  • National Institutes of Health: $625,274.00
  • National Institutes of Health: $525,399.00

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Transplantation
Islets of Langerhans Transplantation
Pancreas
Tissue Donors
Organized Financing
Transplants
Islets of Langerhans
Diabetes Mellitus
Type 1 Diabetes Mellitus
Insulin
Apoptosis
Organ Preservation
Cytoprotection
Clinical Trials
Chimerism
Rodentia
Nitric Oxide
Cell Death
Necrosis
Therapeutics

ASJC

  • Medicine(all)