Encapsulation of Human Islets Using a Biomimetic Self-Assembled Nanomatrix Gel for Protection against Cellular Inflammatory Responses

Abstract

The major concern of pancreatic islet transplantation is that the implanted islets are exposed to the immune system of the recipient. To overcome this challenge, the peptide amphiphile (PA) nanomatrix gel was used for immunoisolation of islets through microencapsulation. The PA can self-assemble to form a nanomatrix gel with an extracellular matrix-mimicking, islet nurturing microenvironment and a semipermeable immune barrier. In this study, the islet protective effect of the PA nanomatrix gel was evaluated by coculture of PA-encapsulated human islets with differentiated U937 cells (human monocyte cell-line) for 3 and 7 days. The coculture of the bare islets with the differentiated U937 cells stimulated proinflammatory cytokine (IL-1β and TNF-α) secretion and caused islet death after 7 days, which simulated an early inflammatory response environment after islet transplantation. The PA-encapsulated islets, however, did not stimulate proinflammatory cytokine secretion and maintained islet viability up to 7 days. More insulin-producing β cells were observed when islets were PA-encapsulated than control islets with the differentiated U937 cells for 7 days compared to the bare islets. This result was also confirmed by dithizone staining analysis. Further evaluation of islet functionality was assessed by a glucose-stimulated insulin secretion test. The PA-encapsulated islets showed greater insulin secretion response to glucose stimulation than the bare islets with the differentiated U937 cells after 3 and 7 days. These results demonstrated that islet encapsulation with the PA nanomatrix gel was able to improve islet survival and function in the presence of inflammatory responses, which will increase the success rate of islet engraftment and the efficacy of islet transplantation.

Evaluation of Viscoelastic Properties, Blood Coagulation, and Cellular Responses of a Temperature-Sensitive Gel for Hemostatic Application

“…32 Human U937 monocytes (Lonza Inc.; Basel, Switzerland) were cultured under biological conditions (37 °C, 5% CO 2 ) in RPMI 1640 media containing 10% fetal bovine serum and 1% penn/strep/ amphotericin (all purchased from Corning Cellgro; Corning, NY). 33 Cytotoxicity Test of Temperature-Sensitive Gels with Coagulation Agent. First, 400 μL of 22 wt % copolymer solutions with and without fibrinogen were prepared in insert wells (Corning; Corning, NY) according to previously established procedures.…”

An Overview of Engineered Hydrogel-Based Biomaterials for Improved β-Cell Survival and Insulin Secretion

“…In another study, Huanget al have fabricated a peptide amphiphile-based nanomatrix hydrogel to encapsulate islets. GSIS showed that cells’ encapsulation almost increased 8,477.78 µIU in glucose-responsive value when exposed to high glucose concentration ( Huang et al, 2017 ). • Other pre-fabricated chemical and physical hydrogels …”

Self-Assembling Peptides as an Emerging Platform for the Treatment of Metabolic Syndrome

“…107 This result is in good agreement with previous research showing the key role that RGD-functionalized Nanomatrix had in improving the biological functions of murine insulin-producing cells in vitro. 108 Another approach evaluated the positive effect that nitric oxide (NO) had on the viability and functions of murine β-cells after being released from Nanomatrix. Therefore, this hydrogel was designed from two functionalized peptides, the first one linking YIGSR and the second one offering a polylysine NO donor linked to a metalloproteinase-2 (MPP-2) biodegradable site to allow NO delivering in a well-controlled manner.…”

“… 107 This result is in good agreement with previous research showing the key role that RGD-functionalized Nanomatrix had in improving the biological functions of murine insulin-producing cells in vitro. 108 …”