Impact of Oxygen on Pancreatic Islet Survival

Abstract

Pancreatic islet transplantation is a promising treatment option for individuals with type 1 diabetes; however, maintaining islet function after transplantation remains a large challenge. Multiple factors, including hypoxia associated events, trigger pretransplant and posttransplant loss of islet function. In fact, islets are easily damaged in hypoxic conditions before transplantation including the preparation steps of pancreas procurement, islet isolation, and culture. Furthermore, after transplantation, islets are also exposed to the hypoxic environment of the transplant site until they are vascularized and engrafted. Because islets are exposed to such drastic environmental changes, protective measures are important to maintain islet viability and function. Many studies have demonstrated that the prevention of hypoxia contributes to maintaining islet quality. In this review, we summarize the latest oxygen-related islet physiology, including computational simulation. Furthermore, we review recent advances in oxygen-associated treatment options used as part of the transplant process, including up-to-date oxygen generating biomaterials as well as a classical oxygen inhalation therapy.

Delivery of shRNA via lentivirus in human pseudoislets provides a model to test dynamic regulation of insulin secretion and gene function in human islets

“…Considering that the loss of human islets during prolonged culture is associated with stresses including inflammation (Negi et al 2012) and hypoxia (Komatsu et al 2018), we tested genes known to be increased in beta cells under inflammation (IL1B, CCL2, and CXCL8), ER stress (TXNIP (Shalev 2014), DDIT3), and hypoxia (HIF1A). There was a significant reduction in expression levels of proinflammatory markers IL1B, CCL2, and CXCL8 for pseudoislets compared with fresh islets (Fig.…”

Human mesenchymal stem cells–derived conditioned medium inhibits hypoxia‐induced death of neonatal porcine islets by inducing autophagy

“…However, present clinical porcine islet transplantation protocols are inefficient. Currently, up to 70% of functional islets are destroyed due to hypoxia‐induced damage during the transplantation process . It is well established that pancreatic islets are sensitive to hypoxia and easily become apoptotic and necrotic under hypoxic conditions .…”

Polymeric Approaches to Reduce Tissue Responses Against Devices Applied for Islet-Cell Encapsulation

“…It is well known that alginate which is not sufficiently purified may provoke stronger tissue responses than purified alginates (Liu et al, 2011; Fang et al, 2017b). We but also others (Tomei et al, 2014; Manzoli et al, 2017, 2018; Buchwald et al, 2018a) do not see severe responses against small capsules and also recognize that larger diameters for capsules also implies lower oxygen supply to the islets (Tomei et al, 2014; Manzoli et al, 2017; Buchwald et al, 2018a; Komatsu et al, 2018; Tomei, 2018) which unfortunately is not discussed in the Veisah study (Veiseh et al, 2015). For this reason, we prefer and keep on working on smaller capsules (Spasojevic et al, 2014a; Paredes-Juarez et al, 2015; Llacua et al, 2018a,c) which will be further discusses in the next sections.…”