Nanotechnology Approaches to Modulate Immune Responses to Cell-based Therapies for Type 1 Diabetes

Abstract

Islet transplantation is a promising curative treatment option for type 1 diabetes (T1D) as it can provide physiological blood glucose control. The widespread utilization of islet transplantation is limited due to systemic immunosuppression requirements, persisting graft immunodestruction, and poor islet engraftment. Traditional macro- and micropolymeric encapsulation strategies can alleviate the need for antirejection immunosuppression, yet the increased graft volume and diffusional distances imparted by these coatings can be detrimental to graft viability and glucose control. Additionally, systemic administration of pro-engraftment and antirejection therapeutics leaves patients vulnerable to adverse off-target side effects. Nanoscale engineering techniques can be used to immunocamouflage islets, modulate the transplant microenvironment, and provide localized pro-engraftment cues. In this review, we discuss the applications of nanotechnology to advance the clinical potential of islet transplantation, with a focus on cell surface engineering, bioactive functionalization, and use of nanoparticles in T1D cell-based treatments.

Wearable Glucose Monitoring and Implantable Drug Delivery Systems for Diabetes Management

“…Besides requirements for robust physical and mechanical designs to facilitate facile implantation, monitor, and possibly retrieve, the encapsulation needs to have excellent biocompatibility for long‐term safety profiles and selective permeation. [ 140,196,197 ] The encapsulation needs to create and maintain a local environment that allows the exchange of nutrients, metabolic molecules, and waste while rejecting the immune mediating cells (i.e., complement, immunoglobulins, cytokines). [ 198 ] Such immuno‐isolation or immune‐stealth properties can relieve patients of islets implant from burdens of life‐long immunosuppression regimen or concerns of possible rejection or failure.…”

Local Immunomodulatory Strategies to Prevent Allo‐Rejection in Transplantation of Insulin‐Producing Cells

“…[ 135 ] Adding immunomodulatory aryl hydrocarbon receptor (AhR) ligand 2‐(1′H‐indole‐3′‐carbonyl)‐thiazole‐4‐carboxylic acid methyl ester (ITE) and T1D autoantigen proinsulin to gold nanoparticle carriers effectively prevented diabetic onset in NOD mice and has been suggested for applications in islet cell graft tolerance. [ 20 , 136 ] Additionally, the targeted delivery of cyclosporine A using polylactide nanoparticles has also shown immunosuppressive effects, though this remains to be explored within the context of islet transplantation. [ 137 ] Many tolerogenic approaches for local graft acceptance involve the use of immunoisolating barriers and are considered as cell encapsulation, which falls outside the scope of this open‐system review but is covered in a rich body of literature.…”

“…[13][14][15] To address these limitations, research is being conducted to induce local immunotolerance, as an alternative approach to systemic immune suppression, to prevent allo-rejection against islets, and stem cell derived 𝛽 (SC-𝛽) cells without encapsulation. [16][17][18][19][20] Local immunotolerance is defined as the lack of a destructive immune response against foreign cells or specific antigens in local areas while retaining the full capacity of the immune system to react to other foreign antigens. [21] For advanced treatment of T1D with extensive 𝛽 cell destruction, cell replacement therapy can, in principle, be applied in combination with local immunomodulatory or tolerogenic approaches to en-able immunological acceptance of the graft.…”

Islet cell encapsulation – Application in diabetes treatment

“…40 One merit of nanoencapsulation is the profound reduction in transplant volume achieved by virtually eliminating the void space between the islet and encapsulating membrane. 39 Elimination of the void space also improves glucose-insulin response time 41 and increases oxygen delivery to islets. Reduction in graft size also has the potential to allow for islet transplantation in narrow spaces like the portal vein which is commonly used as a transplantation site for unencapsulated islets.…”