Islet grafting and imaging in a bioengineered intramuscular space

Piotr Witkowski, Hugo Sondermeijer, Mark A. Hardy, David C. Woodland, Keagan Lee, Govind Bhagat, Kajetan Witkowski, Fiona See, Abbas Rana, Antonella Maffei, Silviu Itescu, Paul E. Harris

Research output: Contribution to journalArticlepeer-review

29 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1065-1074
Number of pages10
JournalTransplantation
Volume88
Issue number9
DOIs
StatePublished - Nov 2009
Externally publishedYes

Keywords

  • Bioengineering.
  • Imaging
  • Islet transplantation

ASJC Scopus subject areas

  • Transplantation

Fingerprint

Dive into the research topics of 'Islet grafting and imaging in a bioengineered intramuscular space'. Together they form a unique fingerprint.

Cite this