Figure - available via license: Creative Commons Attribution 4.0 International
Content may be subject to copyright.
Source publication
The clinical success rate of islet transplantation, namely independence from insulin injections, is limited by factors that lead to graft failure, including inflammation, acute ischemia, acute phase response, and insufficient vascularization. The ischemia and insufficient vascularization both lead to high levels of oxidative stress, which are furth...
Contexts in source publication
Context 1
... this study, we investigate the cell-biomaterial interaction using a series of different polymers with particular attention given to oxidative stress and islet function in rodent pancreatic endocrine cells because they have a transcriptional profile very similar to human islets [38] and are a good model to investigate cell-biomaterial interactions and in vitro characterization of the biomaterials for islet encapsulation [39,40]. All biomaterials studied are considered to be biocompatible based on past performance in in vivo studies and, in some cases, their current clinical use (Table 1). We hypothesize that different polymeric biomaterials can induce different levels of oxidative stress in the blood glucose-controlling pancreatic endocrine cells. ...Context 2
... thermoplastic polymers were preselected on the basis of their past performance and, in some cases, their clinical use (Table 1). The ideal biomaterial for an encapsulation device would be elastic for implantation and hydrophilic to enhance insulin and glucose diffusion [24]. ...Context 3
... testing was performed with the biomaterials in the directions parallel ( Fig. 1) and perpendicular (Supplementary Figure 1) to film casting. Both directions (Supplementary Table 1-2) showed similar statistically significant results. For peak stress, PET and PEOT/PBT4000 had the highest values of 14.4 and 14.7 MPa, respectively (Fig. 1A). ...Citations
... However, efforts have been made to find alternatives to alginate, among which PEOT/PBT300 stands out recently. Sthijns et al. (2021), indicated that PEOT/PBT300 showed the best results compared to other biomaterials, considering its properties of elasticity and resistance to breakage, unaffected gene expression related to angiogenesis, low levels of oxidative stress, expression of endogenous antioxidants, and viability and functionality of pancreatic beta and alpha cells. Thus, PEOT/PBT300 was demonstrated to be a promising polymer for cell encapsulation. ...
Microencapsulation of β-cells is a rapidly growing field that offers broad potential for the therapy and possible cure of diabetes, especially type 1 diabetes, thanks to the immunization of the engrafted tissue that increases its long-term efficacy and decreases the risk of immunogenicity. Despite the promising results obtained in human and animal studies, important challenges need to be addressed. The structure and composition of the microspheres and the site where they are implanted can affect the effectiveness of the treatment, and associated immunogenicity problems have been reported. To improve the safety of the encapsulated islet graft system, new efforts are being made in the bioengineering of the capsules and the production of insulin-producing cells within the capsular membranes. These critical advances in cell encapsulation technology are expected to enable broader and more effective human application of this system. In this review, the great potential of encapsulated pancreatic islet transplantation to provide a cure for type 1 diabetes is highlighted. The advantages and disadvantages of this therapeutic strategy are also outlined, as well as key advances made in cellular microencapsulation research for treating diabetes.
... There are numerous factors that limit success rate of islet transplantation therapy [39] including unsuitable islet microenvironment, loss of vascular connections [40,41], disruption of cell-matrix contacts, and oxidative stress that occur during isolation procedure [42,43]. Adding biomaterials having necessary factors and proteins that are naturally existing in normal islet's niche may be a useful method to improve islet quality and graft success via imitating the biochemical interactions or decreasing oxidative stress. ...
... There are numerous factors that limit success rate of islet transplantation therapy [39] including unsuitable islet microenvironment, loss of vascular connections [40,41], disruption of cell-matrix contacts, and oxidative stress that occur during isolation procedure [42,43]. Adding biomaterials having necessary factors and proteins that are naturally existing in normal islet's niche may be a useful method to improve islet quality and graft success via imitating the biochemical interactions or decreasing oxidative stress. ...
Background:
Loss of islet survival and function, caused by native niche disruption and oxidative stress induction during mechanical and enzymatic isolation, limits the effectiveness of islet transplantation. Reconstitution of islet microenvironment, vascularization, and decreased oxidative stress with biomaterials may improve islet quality and graft outcomes. We investigated effects of two biomaterials, platelet-rich plasma and pancreatic islets homogenate combination on islet recovery and quality by evaluating in vitro islet survival, secretory function, and oxidative stress parameters and assessing in vivo transplantation outcomes.
Methods:
In vitro, islet viability and secretory function of isolated islets were assessed after 24 h and 72 h incubation with biomaterials. Also, oxidative stress markers were measured once after isolation and 24 h after incubation with biomaterials. For evaluating in vivo effects, cultured islets for 24 h were transplanted into subscapular space of diabetic rat kidney, and outcomes were analyzed by measuring serum glucose and insulin concentrations, glucose tolerance test, level of oxidative parameters, and pancreatic gene expression.
Results:
Treating islets with biomaterials significantly increased their viability and secretory function, reduced MDA level, and elevate SOD and CAT activity. Decreased level of glucose and MDA improved insulin level, increased SOD activity, and also enhanced pdx1 and insulin gene expression in diabetic rats after islet transplantation.
Conclusions:
Biomaterials used in the present study should be consider as beneficial materials for increasing islet transplantation outcome. These materials may hamper transplantation limitation to some extent.
... Many functional and effective alternative biomaterials can still be produced via a green approach for different biomedical applications. The search for new materials with excellent immunoprotective functions such as enhancement in protective endogenous antioxidants and noninterference with oxidative stress levels [84] is still an ongoing research area. The optimum conductivity-biocompatibility balance of polyaniline (PANI)-based biomaterials is required for effective marketing, engineering, and application of PANI-based materials in today's world [85]. ...
Biomaterials research has gained considerable momentum recently. The development of technology and the changing human lifestyles have also changed human health needs. The developed materials for use in different areas like in medical products and living bodies have necessitated adding biocompatibility to the mechanical, physical, and chemical properties of these materials. This article is a review of the concept and evaluation of biocompatibility. It explains how biomaterials change with the development of technology, human changing lifestyles, and needs, and how these materials are developed with the same technology. It contains what biocompatibility is, the factors that affect biocompatibility, what can happen in case of low biocompatibility, and the standards and work plans required for tests such as hemocompatibility, genotoxicity, toxicokinetic, and immunotoxicology for biocompatibility..
... This connection becomes stronger, especially in people who are overweight or have impaired fasting glucose tolerance [4]. The results of a study by Sthijns et al., in 2020 showed that increasing reactive oxygen species (ROS) and stabilizing OS could lead to impaired glucose uptake by muscle and adipose tissue and reduced insulin secretion from beta cells [5]. Many drugs are used to control and treat prediabetes, such as Biguanides, sulfonylureas, alpha glucosidase inhibitors and GLP1 analogues [6]. ...
... Controlling blood sugar has reduced mortality and increased life expectancy, but there are still many patients who suffer from long-term complications of the disease, so, preventing pre-diabetes to diabetes is more important to prevent chronic complications [21]. Recent studies have shown that IR, oxidative stress, and inflammation worsen a patient's glycemic status [5]. On the other hand, receiving dietary foods and supplements with antioxidant potential, by increasing insulin sensitivity, improving the state of oxidative stress to antioxidants and reducing inflammation, causes better control of blood sugar [2]. ...
... The final results of their study indicated that consumption of OEA caused a significant decrease in IL6 and TNFα levels [16]. Various scientific investigations show that inflammatory factors play an important role in creating and increasing IR [5]. Increased CRP concentrations have been reported in people with prediabetes [31]. ...
Background
The anti-inflammatory properties of cannabinoids have been shown. This study was conducted to assess effect of oleoylethanolamide (OEA) supplementation on glycemic status, insulin resistance (IR) and inflammatory factor in pre-diabetic individuals.
Methods
This double-blind randomized clinical trial was done at Qazvin University of Medical Sciences in which 46 pre-diabetic patients were divided into two equal groups and received one 125 mg OEA capsule in the intervention group (23 subjects) and 125 mg capsule containing wheat flour in placebo group daily for 8 weeks. After collecting demographic information, at the beginning and end of the study, the questionnaires of physical activity, 24-hour food recall were completed and blood glucose (BG), plasma insulin level, IR, hemoglobin A 1 c (HbA 1 c), and C-reactive protein (CRP) were measured. Statistical analysis was performed using SPSS software.
Results
At the beginning and end of the study, there was no significant difference between the two groups in terms of anthropometric indices, food intake and physical activity (P > 0.05). At the end of the study, consumption of OEA significantly reduced BS, insulin, IR, HbA 1 c, and CRP (P < 0.05). No significant change was observed in mentioned biochemical factors in placebo group (P > 0.05).
Conclusions
Given that OEA supplementation improved the glycemic status, IR and reduced the inflammatory factor, use of this supplement can be introduced as a useful supplement to control pre-diabetes status.
Trial registration : The protocol of this clinical trial is registered with the Iranian Registry of Clinical Trials ( http://www.IRCT.IR , identifier: IRCT20141025019669N16).
... As a future outlook, it would be interesting to validate this finding in the context of beta cell replacement strategies, where the cells are known to experience high levels of oxidative stress [31,32,[43][44][45]. Engineered islets could be transplanted in the ratio of 50:50 beta:alpha cells to protect them against the oxidative stress they experience during transplantation and from biomaterials used for encapsulation [46]. This approach becomes a reasonable strategy as the differentiation of pluripotent stem cells into pancreatic endocrine cells can create engineered islets resembling their in vivo counterparts [47]. ...
The pancreatic islets of Langerhans have low endogenous antioxidant levels and are thus especially sensitive to oxidative stress, which is known to influence cell survival and behaviour. As bioengineered islets are gaining interest for therapeutic purposes, it is important to understand how their composition can be optimized to diminish oxidative stress. We investigated how the ratio of the two main islet cell types (alpha and beta cells) and their culture in three-dimensional aggregates could protect against oxidative stress. Monolayer and aggregate cultures were established by seeding the alphaTC1 (alpha) and INS1E (beta) cell lines in varying ratios, and hydrogen peroxide was applied to induce oxidative stress. Viability, oxidative stress, and the level of the antioxidant glutathione were measured. Both aggregation and an increasing prevalence of INS1E cells in the co-cultures conferred greater resistance to cell death induced by oxidative stress. Increasing the prevalence of INS1E cells also decreased the number of alphaTC1 cells experiencing oxidative stress in the monolayer culture. In 3D aggregates, culturing the alphaTC1 and INS1E cells in a ratio of 50:50 prevented oxidative stress in both cell types. Together, the results of this study lead to new insight into how modulating the composition and dimensionality of a co-culture can influence the oxidative stress levels experienced by the cells.
... Biomaterials' selection should considerer their contribution to optimum redox state, as suggested by Sthijns et al. (Sthijns et al., 2021), who evaluated different polymers for a pancreatic islet encapsulation device; cell sensitivity to oxidative stress is variable and essential for cell survival, proliferation, and function (Sthijns et al., 2021), and contributes to avoid chronic inflammation and peri-implantar fibrosis. As reviewed by Sthijns et al. (Sthijns et al., 2018), in tissue engineering approaches, ensuring adequate perfusion of the construct is paramount for cell survival and to avoid increased ROS formation. ...
... Biomaterials' selection should considerer their contribution to optimum redox state, as suggested by Sthijns et al. (Sthijns et al., 2021), who evaluated different polymers for a pancreatic islet encapsulation device; cell sensitivity to oxidative stress is variable and essential for cell survival, proliferation, and function (Sthijns et al., 2021), and contributes to avoid chronic inflammation and peri-implantar fibrosis. As reviewed by Sthijns et al. (Sthijns et al., 2018), in tissue engineering approaches, ensuring adequate perfusion of the construct is paramount for cell survival and to avoid increased ROS formation. ...
Oxidative stress plays a central role in physiological and pathological bone conditions. Its role in signalment and control of bone cell population differentiation, activity, and fate is increasingly recognized. The possibilities of its use and manipulation with therapeutic goals are virtually unending. However, how redox balance interplays with the response to mechanical stimuli is yet to be fully understood. The present work summarizes current knowledge on these aspects, in an integrative and broad introductory perspective.
... In addition, different synthetic polymers have different basic physicochemical properties which can induce stress to islet cells it is therefore important to test the interaction of primary islets and beta cells with these materials prior to their usage in a cell delivery device to ensure a minimal negative effect on survival and function. 22 In this study, we used microscopic evaluation and functional assays to test four selected synthetic polymers for their suitability as a scaffold for islet transplantation. The following synthetic polymers were tested: polyetheretherketone (PEEK), polyvinylidene fluoride (PVDF), polyphenylsulfone (PPSU) and polysulfone (PSU). ...
As a treatment for type I diabetes, clinical islet transplantation (CIT) in which donor islets of Langerhans are transplanted intrahepatically has become a viable option for patients. However, the success of this procedure is limited by factors including ischemia, host immunological factors, and delayed vascularization of the hypoxia-sensitive islets. One solution would be to use a synthetic polymer scaffold as a carrier for the transplanted islets, as it would allow for their transplantation into a more favorable environment and could protect the cells from host immune reactions. To realize this potential solution, it is important that the synthetic polymer used does not interfere with the functionality and survival of the islets. In order to determine which synthetic polymers best meet this requirement, we examined the interactions of human islets from six donors with four clinically approved materials: polyetheretherketone (PEEK), polyvinylidene fluoride (PVDF), polyphenylsulfone (PPSU) and polysulfone (PSU) in vitro. Human islet morphology, viability, insulin secretion, functionality and gene expression were investigated to assess the suitability of these synthetic polymers as a carrier for transplanted islets. We found three of the synthetic synthetic polymers (PEEK, PPSU and PVDF) showed promise based on their overall performance, while the glucose responsiveness of islets cultured on PSU resulted in significantly reduced insulin secretion from five of six donors. Our findings demonstrate that close examination of human islets and their interaction with synthetic polymers is an important factor to consider when selecting synthetic polymers for engineering islet replacement devices.
Type 1 diabetes is a life-threatening disease that is hallmarked by an autoimmune response against the insulin-producing β-cells in the pancreatic islets. Currently, clinical islet transplantation is the most promising minimal invasive therapy to treat the most severe cases of type 1 diabetes. Despite great progress in islet isolation and transplantation protocols in the last two decades, most patients are required to switch back to exogeneous insulin administration after several years post-transplantation. Bioengineering approaches through encapsulation of islets, or stem cell-derived β-cells, can be used to support cells or offer novel implantation sites that could potentially improve the outcome of clinical islet transplantation. However, the selection of biomaterials for cell delivery is challenging since the tissue response to an implant can be influenced by a wide range of biomaterial characteristics. This chapter will therefore discuss the influence of biomaterial characteristics such as chemical composition, porosity, topography, mechanical properties, degradability, and functionalization on biomaterial biocompatibility. In addition, the importance of clean fabrication techniques and selection of biomaterials that allow for non-invasive monitoring of cell grafts are highlighted.
Oxidative stress leads to a lower success rate of clinical islet transplantation. Here, FDA‐approved compounds are screened for their potential to decrease oxidative stress and to protect or enhance pancreatic islet viability and function. Studies are performed on in vitro “pseudoislet” spheroids, which are pre‐incubated with 1280 different compounds and subjected to oxidative stress. Cell viability and oxidative stress levels are determined using a high‐throughput fluorescence microscopy pipeline. Initial screening on cell viability results in 59 candidates. The top ten candidates are subsequently screened for their potential to decrease induced oxidative stress, and eight compounds efficient reduction of induced oxidative stress in both alpha and beta cells by 25–50%. After further characterization, the compound sulfisoxazole is found to be the most capable of reducing oxidative stress, also at short pre‐incubation times, which is validated in primary human islets, where low oxidative stress levels and islet function are maintained. This study shows an effective screening strategy with 3D cell aggregates based on cell viability and oxidative stress, which leads to the discovery of several compounds with antioxidant capacity. The top candidate, sulfisoxazole is effective after a 30 min pre‐incubation, maintains baseline islet function, and may help alleviate oxidative stress in pancreatic islets.
