Preface - Ous-research.no

Cell Transplantation
ted source for xenotransplantation, still, IBMIR and other
factors that hamper the success of allo-islet transplantation
will remain. The intramuscular site allows manipulation of
the graft and the implantation site prior to transplantation
and could easily be excised if necessary (Fig. 5 ). We have
shown that islet transplantation into striated musculature
is feasible, however, in its present form the intramuscular
site is less efficient compared to the liver. Ex vivo manipulation
of islets is discussed, especially coating of the islets
with mesenchymal and endothelial cells from the recipient
and thus reducing the antigen presentation of islets after
transplantation. Explorative studies on striated musculature
as a potential site for islet transplantation is defined in a PhD
program (Kristine Kloster-Jensen).
Project 4. In vivo surveillance of transplanted islets
Transplanted islet cell mass is not static but changes in
response to the environment, e.g. inflammation at the transplant
site, toxicity of immunosuppressants and influence by
the immune system. Non-invasively monitoring of changes
in islet mass following islet transplantation is important to
provide new insight into factors regulating post transplant
function. The research group is exploring two different approaches
for post transplant islet mass surveillance.
4.1 Bioluminescent in vivo imaging
Recently, in collaboration with the Transplantation Research
Laboratory, UCSF (Dr. Hanne Scholz) the transgenic mouse
stock, insulin I promoter (MIP-luc) has been imported to our
laboratory. In these mice, luciferase-expressed beta cells is
visualized by bioluminescent imaging and has been shown
to correlate with beta cell mass (Fig. 6 ). Thus, this non-invasive
model can be utilized to monitor changes in beta-cell
mass over time in individual animals. The bioluminescent
imaging technique is an important tool for the research
in islet transplantation, and is implicated in many of the
ongoing studies.
4.2 PET in vivo imaging
Pancreatic islet cell engraftment, distribution, function
and survival can be visualized by PET in vivo imaging. The
application of the PET technology in clinical islet transplantation
takes advantage of the recent rapid development of
non-invasive imaging technology in a new area of medicine.
The aim of this project is to obtain a new unique method to
acquire detailed knowledge of the engraftment process of
intraportal implanted islets in man.
Hepatocytes
General objectives
Uppsala university/Karolinska institute/Oslo University
(Institute for Surgical Research)
••
Approaches to overcome the Instant Blood-Mediated
Inflammatory Reaction (IBMIR) induced by hepatocytes at
the time of transplantation.
••
Enhancement of hepatocyte engraftment by LMW-DS
induced HGF
••
Development of a clinically applicable imaging technique
for the evaluation of hepatocyte engraftment.
Figure 6. Bioluminescent in vivo imaging.
Background
Whole organ liver transplantation (Ltx) is standard clinical
treatment for patients with acute and chronic liver diseases
and even for selected patients with primary and secondary
liver tumors. However, due to organ shortage a significant
number of patients are dying on the waiting list. Several
initiatives such as split-liver (one liver for two recipients) and
live donor transplantation have been introduced to reduce
the waiting lists for Ltx. However, additional approaches are
necessary to overcome pretransplant mortality. Experimental
studies and some clinical trials have shown that hepatocyte
transplantation may be useful in patients as a bridge to
Ltx or while waiting for the liver to regenerate (acute toxic
liver failure). In selected patients with single enzymatic defects,
hepatocyte transplantation may even heal the disease.
More than 200 patients with acute and chronic liver failure
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