Assessing the Effects of VEGF Releasing Microspheres on the Angiogenic and Foreign Body Response to a 3D Printed Silicone-Based Macroencapsulation Device

Macroencapsulation systems have been developed to improve islet cell transplantation but can induce a foreign body response (FBR). The development of neovascularization adjacent to the device is vital for the survival of encapsulated islets and is a limitation for long-term device success. Previously we developed additive manufactured multi-scale porosity implants, which demonstrated a 2.5-fold increase in tissue vascularity and integration surrounding the implant when compared to a non-textured implant. In parallel to this, we have developed poly(ε-caprolactone-PEG-ε-caprolactone)-b-poly(L-lactide) multiblock copolymer microspheres containing VEGF, which exhibited continued release of bioactive VEGF for 4-weeks in vitro. In the present study, we describe the next step towards clinical implementation of an islet macroencapsulation device by combining a multi-scale porosity device with VEGF releasing microspheres in a rodent model to assess prevascularization over a 4-week period. An in vivo estimation of vascular volume showed a significant increase in vascularity (* p = 0.0132) surrounding the +VEGF vs. −VEGF devices, however, histological assessment of blood vessels per area revealed no significant difference. Further histological analysis revealed significant increases in blood vessel stability and maturity (** p = 0.0040) and vessel diameter size (*** p = 0.0002) surrounding the +VEGF devices. We also demonstrate that the addition of VEGF microspheres did not cause a heightened FBR. In conclusion, we demonstrate that the combination of VEGF microspheres with our multi-scale porous macroencapsulation device, can encourage the formation of significantly larger, stable, and mature blood vessels without exacerbating the FBR.

P-P41 Systematic review of Sarcopenia in Chronic Pancreatitis: prevalence, impact on surgical outcomes and survival

Background Chronic pancreatitis(CP) is characterised by progressive inflammatory changes to the pancreas, leading to loss of endocrine and exocrine function. Emerging literature suggests sarcopenia may adversely affect outcomes for chronic pancreatitis patients. This systematic review examines the evidence surrounding the impact of sarcopenia on patients with CP. Methods A systematic literature search of PUBMED, MEDLINE and EMBASE databases identified articles describing body composition assessment in patients with CP. Data collected included definitions of sarcopenia, assessment methodology, baseline demographics, surgery related data and short- and long-term outcomes. Results 9 studies, including 977 patients and a sarcopenia prevalence of 32.3% were included. Alcohol was the predominant aetiology. There was significant heterogeneity in definitions of sarcopenia used. CT was the main modality to assess for sarcopenia in 7 papers, MRI in 2 papers and clinical measurements in 2 papers. 2 papers included patients undergoing total pancreatectomy and Islet cell transplantation. None of the studies found a significant increase in complications with sarcopenia. 1 Year mortality in outpatients from one study of patients with CP was 16% in sarcopenic patients versus 3% (HR:6.69(95%CI:1.79–24.9),p<0.001). Conclusions Sarcopenia is prevalent in patients with CP and has adverse impact on short- and long-term survival.

The Feasibility and Applicability of Stem Cell Therapy for the Cure of Type 1 Diabetes

Stem cell therapy using islet-like insulin-producing cells derived from human pluripotent stem cells has the potential to allow patients with type 1 diabetes to withdraw from insulin therapy. However, several issues exist regarding the use of stem cell therapy to treat type 1 diabetes. In this review, we will focus on the following topics: (1) autoimmune responses during the autologous transplantation of stem cell-derived islet cells, (2) a comparison of stem cell therapy with insulin injection therapy, (3) the impact of the islet microenvironment on stem cell-derived islet cells, and (4) the cost-effectiveness of stem cell-derived islet cell transplantation. Based on these various viewpoints, we will discuss what is required to perform stem cell therapy for patients with type 1 diabetes.

Total Pancreatectomy with Autologous Islet Cell Transplantation—The Current Indications

Total pancreatectomy is a major complex surgical procedure involving removal of the whole pancreatic parenchyma and duodenum. It leads to lifelong pancreatic exocrine and endocrine insufficiency. The control of surgery-induced diabetes (type 3) requires insulin therapy. Total pancreatectomy with autologous islet transplantation (TPAIT) is performed in order to prevent postoperative diabetes and its serious complications. It is very important whether it is safe and beneficial for patients in terms of postoperative morbidity and mortality, and long-term results including quality of life. Small duct painful chronic pancreatitis (CP) is a primary indication for TPAIT, but currently the indications for this procedure have been extended. They also include hereditary/genetic pancreatitis (HGP), as well as less frequent indications such as benign/borderline pancreatic tumors (intraductal papillary neoplasms, neuroendocrine neoplasms) and “high-risk pancreatic stump”. The use of TPAIT in malignant pancreatic and peripancreatic neoplasms has been reported in the worldwide literature but currently is not a standard but rather a controversial management in these patients. In this review, history, technique, indications, and contraindications, as well as short-term and long-term results of TPAIT, including pediatric patients, are described.