PracticeUpdate: Conference Series | ADC 2018

Biodegradable TemporisingMatrix as an Alternative Intracutaneous Site for Islet Transplantation BY TOBY COATES MBBS, PhD, FRACP & JOHN GREENWOOD MBCHB, MD, DHLTHSC, FRCS(ENG), FRCS(PLAST), FRACS

Dr. Toby Coates Dr. John Greenwood Dr. Coates is Professor of Medicine and Director of Kidney and Pancreatic Islet Transplantation at the University of Adelaide, Royal Adelaide Hospital in Adelaide, South Australia. Dr. Greenwood is Director of the Adults Burns Unit at the Royal Adelaide Hospital in Adelaide, South Australia. O ne of themain barriers to the greater use of cell therapies to treat type 1 diabetes (T1D) is the current transplant site. Islet transplantation as it is currently practiced requires the infusion of allogeneic islets, derived from donor pancreas, into the liver of patients with T1D under immunosuppression. It is estimated that up to 75% of transplanted islets are lost in the first 48 hours due to poor revascularization within the liver microenvironment. As a result, many patients require two or more islet infusions to achieve insulin independence. Transplantation into the skin has been considered a potential alternative to liver transplantation, which has previously been unsuccessful due to the native skin’s poor vascularization. The Biodegradable Temporising Matrix (BTM) is a polyurethane foam which has recently received TGA approval for use in wounds. The BTM, when implanted, creates a highly vascularized “neo dermis” in the intracutaneous site. In preclinical models, islets transplanted into the BTM showed normal function. When transplanted into large animal models, porcine and human islets were able to regulate glucose responses from the intracutaneous site and respond to an intravenous glucose challenge. The translational implications of an intracutaneous site for islet transplantation revolve around being able to image the islet transplant as well as biopsy the site to diagnose transplant rejection. Both of these clinical management strategies have

However, plasma acetate does not seem to have potential as a biomarker as its lev- els were not different in participants with T1D or with two or more islet antibodies versus controls. “Progressors to type 1 diabetes have higher small intestinal permeability, altered diversity, lower richness and less anti-in- flammatory bacteria than non-progressors. Interestingly, lower gut microbiome richness correlated with lower plasma acetate,” Professor Couper said. She added that the inter-relationship among intestinal permeability, short-chain fatty acids, and microbial diversity pro- vided original human data supporting a mechanism for progression to T1D. “The discovery of a low abundance of anti-inflammatory species in type 1 diabetes and at-risk children require deeper sequencing to look at the poten- tial for bespoke probiotic development to reduce the progression rate to T1D,” she said.

not been possible with conven- tional intraportal administration. Furthermore, an intracutaneous site may be completely removed, allowing newer stem cell or xeno- geneic islet-based technologies to translate into the clinic. Finally, the dense vascular network created by the BTM has the potential to house other endocrine cells, such as adrenal or parathyroid cells, to make treatment of other endocrine deficiency disorders by cell therapies a clinical reality.

www.practiceupdate.com/c/73013

www.practiceupdate.com/c/73017

© Australian Diabetes Society

ADC 2018 • PRACTICEUPDATE CONFERENCE SERIES 13