Islet grafting and imaging in a bioengineered intramuscular space.
BACKGROUND
Because the hepatic portal system may not be the optimal site for islet transplantation, several extrahepatic sites have been studied. Here, we examine an intramuscular transplantation site, bioengineered to better support islet neovascularization, engraftment, and survival, and we demonstrate that at this novel site, grafted beta cell mass may be quantitated in a real-time noninvasive manner by positron emission tomography (PET) imaging.


METHODS
Streptozotocin-induced rats were pretreated intramuscularly with a biocompatible angiogenic scaffold received syngeneic islet transplants 2 weeks later. The recipients were monitored serially by blood glucose and glucose tolerance measurements and by PET imaging of the transplant site with [11C] dihydrotetrabenazine. Parallel histopathologic evaluation of the grafts was performed using insulin staining and evaluation of microvasularity.


RESULTS
Reversal of hyperglycemia by islet transplantation was most successful in recipients pretreated with bioscaffolds containing angiogenic factors when compared with those who received no bioscaffolds or bioscaffolds not treated with angiogenic factors. PET imaging with [11C] dihydrotetrabenazine, insulin staining, and microvascular density patterns were consistent with islet survival, increased levels of angiogenesis, and with reversal of hyperglycemia.


CONCLUSIONS
Induction of increased neovascularization at an intramuscular site significantly improves islet transplant engraftment and survival compared with controls. The use of a nonhepatic transplant site may avoid intrahepatic complications and permit the use of PET imaging to measure and follow transplanted beta cell mass in real time. These findings have important implications for effective islet implantation outside of the liver and offer promising possibilities for improving islet survival, monitoring, and even prevention of islet loss.
Witkowski
Piotr
P
Department of Surgery, Columbia University Medical College, New York, NY, USA. pw2004@columbia.edu
Sondermeijer
Hugo
H
Hardy
Mark A
MA
Woodland
David C
DC
Lee
Keagan
K
Bhagat
Govind
G
Witkowski
Kajetan
K
See
Fiona
F
Rana
Abbas
A
Maffei
Antonella
A
Itescu
Silviu
S
Harris
Paul E
PE
D000818:Animals; D001698:Biomedical Engineering; D001786:Blood Glucose / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000601:surgery*; D005951:Glucose Tolerance Test; D007328:Insulin / Q000494:pharmacology; D007515:Islets of Langerhans / Q000098:blood supply; D016381:Islets of Langerhans Transplantation / Q000379:methods*; D008297:Male; D018482:Muscle, Skeletal / Q000601:surgery*; D018919:Neovascularization, Physiologic; D011168:Portal System / Q000601:surgery; D049268:Positron-Emission Tomography; D051381:Rats; D011917:Rats, Inbred Lew; D017207:Rats, Sprague-Dawley; D014185:Transplantation, Isogeneic; D016896:Treatment Outcome
D001786:Blood Glucose; D007328:Insulin