Courtney D Johnson, Helim Aranda-Espinoza, John P Fisher
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Donor islets are encapsulated in a semipermeable hydrogel, allowing the diffusion of oxygen, glucose, and insulin but preventing leukocyte infiltration and antibody access to the transplanted cells. Although successful in small animal models, EIT is still far from commercial use owing to necessary long-term systemic immunosuppressants and consistent immune rejection. Most published research has focused on tailoring the characteristics of the capsule material to promote clinical viability. However, most studies have been limited in scope to biochemical changes. Current mechanobiology studies on the effect of substrate stiffness on the function of leukocytes, especially macrophages-primary foreign body response (FBR) orchestrators, show promise in tailoring a favorable response to tissue-engineered therapies such as EIT. In this review, we explore strategies to improve the clinical viability of EIT. A brief overview of the immune system, the FBR, and current biochemical approaches will be elucidated throughout this exploration. Furthermore, an argument for using substrate stiffness as a capsule design parameter to increase EIT efficacy and clinical viability will be posed.</p>","PeriodicalId":23134,"journal":{"name":"Tissue Engineering. Part B, Reviews","volume":"29 4","pages":"334-346"},"PeriodicalIF":5.1000,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10442690/pdf/","citationCount":"0","resultStr":"{\"title\":\"A Case for Material Stiffness as a Design Parameter in Encapsulated Islet Transplantation.\",\"authors\":\"Courtney D Johnson, Helim Aranda-Espinoza, John P Fisher\",\"doi\":\"10.1089/ten.TEB.2022.0157\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Diabetes is a disease that plagues over 463 million people globally. 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引用次数: 0
摘要
糖尿病是一种困扰全球超过 4.63 亿人的疾病。其中约有 4000 万患者患有 1 型糖尿病(T1DM),全球发病率正以每年高达 5%的速度递增。T1DM 是指人体免疫系统用抗体攻击胰腺,特别是胰腺 beta 细胞,阻止胰岛素分泌。尽管外源性胰岛素注射等现有治疗方法取得了成功,但高昂的胰岛素费用和精细的用药使人们需要寻找其他长期解决方案来解决糖尿病引起的血糖失调问题。包裹胰岛移植(EIT)是一种组织工程糖尿病解决方案。捐献的胰岛被包裹在半透性水凝胶中,允许氧气、葡萄糖和胰岛素扩散,但阻止白细胞浸润和抗体进入移植细胞。虽然 EIT 在小型动物模型中取得了成功,但由于需要长期使用全身性免疫抑制剂和持续的免疫排斥反应,因此距离商业化应用还很遥远。大多数已发表的研究都集中于调整胶囊材料的特性,以提高临床可行性。然而,大多数研究的范围仅限于生化变化。目前关于基质硬度对白细胞功能影响的机械生物学研究,尤其是巨噬细胞--异物反应(FBR)的主要协调者--显示了对组织工程疗法(如 EIT)定制有利反应的前景。在这篇综述中,我们将探讨提高 EIT 临床可行性的策略。在整个探讨过程中将简要概述免疫系统、FBR 和当前的生化方法。此外,我们还将提出将基质硬度作为胶囊设计参数以提高 EIT 疗效和临床可行性的论点。
A Case for Material Stiffness as a Design Parameter in Encapsulated Islet Transplantation.
Diabetes is a disease that plagues over 463 million people globally. Approximately 40 million of these patients have type 1 diabetes mellitus (T1DM), and the global incidence is increasing by up to 5% per year. T1DM is where the body's immune system attacks the pancreas, specifically the pancreatic beta cells, with antibodies to prevent insulin production. Although current treatments such as exogenous insulin injections have been successful, exorbitant insulin costs and meticulous administration present the need for alternative long-term solutions to glucose dysregulation caused by diabetes. Encapsulated islet transplantation (EIT) is a tissue-engineered solution to diabetes. Donor islets are encapsulated in a semipermeable hydrogel, allowing the diffusion of oxygen, glucose, and insulin but preventing leukocyte infiltration and antibody access to the transplanted cells. Although successful in small animal models, EIT is still far from commercial use owing to necessary long-term systemic immunosuppressants and consistent immune rejection. Most published research has focused on tailoring the characteristics of the capsule material to promote clinical viability. However, most studies have been limited in scope to biochemical changes. Current mechanobiology studies on the effect of substrate stiffness on the function of leukocytes, especially macrophages-primary foreign body response (FBR) orchestrators, show promise in tailoring a favorable response to tissue-engineered therapies such as EIT. In this review, we explore strategies to improve the clinical viability of EIT. A brief overview of the immune system, the FBR, and current biochemical approaches will be elucidated throughout this exploration. Furthermore, an argument for using substrate stiffness as a capsule design parameter to increase EIT efficacy and clinical viability will be posed.
期刊介绍:
Tissue Engineering Reviews (Part B) meets the urgent need for high-quality review articles by presenting critical literature overviews and systematic summaries of research within the field to assess the current standing and future directions within relevant areas and technologies. Part B publishes bi-monthly.