Preface - Ous-research.no

Cell Transplantation
Background
Type 1 diabetes is an autoimmune disease with destruction
of insulin producing β cells, leading to dysregulated glucose
homeostasis. Despite effective insulin therapy, allowing
these patients to survive, imperfect blood sugar control may
result in micro-vascular complications. These complications
can to some extent, be prevented by maintaining nearnormal
glucose control by multiple daily insulin injections
or insulin-pump therapy. However, stable metabolic control
is difficult to achieve in some patients despite the use of
modern insulin analogues and delivery systems, resulting in
life threatening episodes of insulin-induced hypoglycemia.
Transplantation of whole organ pancreas is an optional
treatment for type 1 diabetes. A major drawback of the
procedure is the complexity of the surgery and postoperative
complications caused especially by the exocrine
pancreatic tissue. On the opposite, islet cell transplantation
is a simple and gentle procedure with few complications.
It is performed in local anesthesia. A catheter is inserted
trans-hepatically into the main stem of the portal vein.
Purified islets flow by gravity from the infusion bag through
the catheter and are dispersed in the sinusoids throughout
the liver (Fig. 1). Subsequently, a neo-angiogenesis occurs
(engraftment) and the islets begin to produce and release
insulin within two weeks after the transplantation. The patient
remains awake during the entire procedure which lasts
for less than one hour.
Several reports have shown that up to 80% of the patients
transplanted are off insulin one year after islet transplantation,
but only a few remain free from insulin requirement
long term. However, the majority of patients have significant
C-peptide production five years after the transplantation
and thus, many patients who previously were suffering
from life threatening hypoglycemia exhibit well-regulated
metabolic control and improved quality of life.
Multiple deleterious events affect the amount and quality of
islets from the time of ICU-treatment of the donor, through
the processes of brain death, organ retrieval, islet isolation,
infusion and engraftment. Following successful engraftment
islets are influenced by allo- and autoimmunity and
Figure 1. Aspects of islet cell transplantation.
Figure 2.
Schematic presentation of loss of islets from the time of organ
retrieval to revascularization in the recipient.
1. Loss of islets during brain death and organ harvest. 2. Loss of
islets during islet isolation. 3. Loss of islets during pre-transplant
culture. 4. Loss of islets during the islet transplant procedure 5.
Loss of islets during post-transplant period prior to revascularization.
Green area represents insulin-independence, red area
insulin dependence for the patient.
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