Sustained reversal of diabetes following islet transplantation to striated musculature in the rat.
BACKGROUND
There is an increasing emphasis in the islet transplant community on the development of alternative sites for islet implantation. Striated musculature constitutes a potential alternative, which has been successfully employed in autotransplantation of parathyroid glands for decades. In the present study, a technique for intramuscular islet transplantation was developed and compared with intraportal islet transplantation in a syngeneic rat model.


METHODS
Lewis rats were used. Pancreata were digested using Liberase. Islets were either transplanted into m. biceps femoris in a pearls-on-a-string fashion or intraportally, and the ability to reverse diabetes was compared. Eight weeks after transplantation an IVGTT was performed. Real-time quantitative RT-PCR was employed on muscle biopsies to investigate mRNA levels of cytokines in response to the transplant procedure. Explanted livers, muscles, and pancreata were harvested at the end of the experiment for histopathological analyses.


RESULTS
2000 IEQ repeatedly cured diabetic rats at the intraportal site, while 4000 IEQ was required at the intramuscular site. Time to reversal of diabetes, post-transplant weight development, and IVGTT curves did not differ between the groups. Normoglycemia was sustainable to the end of the study (>100 days) for all animals. The transplant procedure upregulated pro-inflammatory cytokines (IL-6 and IL-8) in striated muscle, and peri-islet fibrosis was observed in intramuscular grafts.


CONCLUSIONS
Islet transplantation into striated musculature is feasible; however, in its present form the intramuscular site is less efficient compared with the liver in rats. The intramuscular site allows manipulation of the graft and implantation site prior to transplantation and may therefore have implications for islet transplantation in humans.
Lund
Tormod
T
Surgical Clinic, Section for Transplantation, Rikshospitalet University Hospital, Oslo, Norway. tormod.lund@rikshospitalet.no
Korsgren
Olle
O
Aursnes
Ingrid A
IA
Scholz
Hanne
H
Foss
Aksel
A
D000818:Animals; D003920:Diabetes Mellitus / Q000628:therapy*; D003921:Diabetes Mellitus, Experimental / Q000628:therapy; D005951:Glucose Tolerance Test; D007150:Immunohistochemistry; D007273:Injections, Intramuscular; D007515:Islets of Langerhans / Q000166:cytology*; D016381:Islets of Langerhans Transplantation / Q000379:methods*; D018485:Muscle Fibers, Skeletal / Q000166:cytology* / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011917:Rats, Inbred Lew; D013311:Streptozocin
D012333:RNA, Messenger; D013311:Streptozocin