Another possible cause of marginal effects

Another possible cause of marginal effects of transplanted encapsulated islets was fibrosis of order info after transplantation as indicated in the histology study. Though, the histology study was not performed for quantitative analysis. It was demonstrated that microcapsule could prevent direct contact of neonatal porcine islets by host immune cells, however, shed xeno-antigens might escape from the capsule (Rayat et al., 2000; Kobayashi et al., 2006). This shed xeno-antigen might activate indirect pathway resulted in recruitment of CD4+ T cells and macrophages around the microcapsule. The recruited CD4+ T cells might produce interferon-gamma and interleukin-10 which induced inflammatory reaction. This inflammatory reaction could cause the fibrosis of microcapsule. Prevention of the indirect pathway might improve this issue. In addition, maturation of neonatal islets is one of the important factors for proper insulin secretory ability (Kobayashi et al., 2008). In this study, we did not assess the maturity of neonatal islets before transplantation, however; we plan to assess the maturity of neonatal islets before transplantation for the next clinical trial. Several clinical studies have been reported about encapsulated human allogeneic islet transplantations (Tuch et al., 2009; Jacobs-Tulleneers-Thevissen et al., 2013; Basta et al., 2011), however, insulin independence or significant reduction of insulin doses were rare. The best clinical outcomes were demonstrated by Basta et al. (2011) which showed 4 patients maintained HbA1c<8% at 12months and 24months. In our study, the values of HbA1c in group 2 were <7% >600days. This suggests that healthy porcine islets could provide better function compared with human islets which are usually recovered from deceased donors. In conclusion, encapsulated neonatal porcine islet xenotransplantation could maintain HbA1c<7% with significant reduced hypoglycemic events without immunosuppression >600days. We believe this study is the prologue for the clinical xenotransplantation to solve the issue of donor shortage.
Authors\' Contributions
Conflict of Interest Statements
Role of Funding Source Entire researches have been funded by Living Cell Technologies and Diatranz Otsuka Ltd.
Ethics Committee Approval The study protocol (ClinicalTrials.gov Identifier NCT01739829) was granted ethics approval in Argentina from the Ministry of Health, Buenos Aires Province.
Introduction Diabetes is the most common underlying cause of chronic kidney disease leading to renal failure, accounting for about 40–50% of cases (Tuttle et al., 2014). Although inhibition of the renin-angiotensin aldosterone system can slow progression of diabetic kidney disease, the residual risk of progression to end stage renal failure is high (Lewis et al., 2001; Brenner et al., 2001). Appreciation of the multiple pathways by which progressive kidney injury occurs has led to a search for novel therapeutic approaches to slow, halt or reverse progression of renal disease in type 2 diabetic patients. Research has implicated inflammation as one contributing factor in the pathophysiology of diabetic nephropathy (Wada & Makino, 2013; Navarro-Gonzalez & Mora-Fernandez, 2011; Lim & Tesch, 2012). The anti-inflammatory properties of adult, bone-marrow derived mesenchymal lineage cells may have beneficial effects in diabetic nephropathy, as suggested by observed effects on renal function and histology in animal models of chronic kidney disease (Prockop & Oh, 2012; Singer & Caplan, 2011; Cantaluppi et al., 2013). Other properties such as tropism for damaged tissues and secretion of a broad range of bioactive molecules with subsequent paracrine effects contribute to the effects on renal function and histopathology in preclinical chronic and acute kidney injury models (Papazova et al., 2015; Meirelles Lda et al., 2009; Hickson et al., 2016). In addition, the capacity of this cell type to reprogram macrophages from a proinflammatory M1 phenotype to the alternatively activated or anti-inflammatory M2 phenotype may also promote tissue repair (Maggini et al., 2010; Kim & Hematti, 2009).