Review of Advanced Hydrogel-Based Cell Encapsulation Systems for Insulin Delivery in Type 1 Diabetes Mellitus

Abstract

: Type 1 Diabetes Mellitus (T1DM) is characterized by the autoimmune destruction of β-cells in the pancreatic islets. In this regard, islet transplantation aims for the replacement of the damaged β-cells through minimally invasive surgical procedures, thereby being the most suitable strategy to cure T1DM. Unfortunately, this procedure still has limitations for its widespread clinical application, including the need for long-term immunosuppression, the lack of pancreas donors and the loss of a large percentage of islets after transplantation. To overcome the aforementioned issues, islets can be encapsulated within hydrogel-like biomaterials to diminish the loss of islets, to protect the islets resulting in a reduction or elimination of immunosuppression and to enable the use of other insulin-producing cell sources. This review aims to provide an update on the different hydrogel-based encapsulation strategies of insulin-producing cells, highlighting the advantages and drawbacks for a successful clinical application.

Enabling allogeneic therapies: CIRM-funded strategies for immune tolerance and immune evasion

“…For example, other methods being used to induce immune tolerance include adoptive transfer of cell types such as Tregs, tolerogenic dendritic cells, and mesenchymal stromal cells 34‐36 . In addition, there are many groups working on different ways to encapsulate or otherwise shield grafted cells from the immune response, 29 and to create immune evasive cells 37 . Although many of these approaches are still relatively new and have not yet been implemented clinically, there is great promise that improved methods for enabling engraftment of allogeneic cells, organs, or tissues will enable much broader use of regenerative therapies as they are developed.…”

“…Among the strategies to avoid the immune system, encapsulation is perhaps conceptually the simplest way to protect a cellular therapeutic while at the same time being the most limited in its application. Both microencapsulation devices, in which relatively small numbers of cells are embedded in matrices such as alginate, polyethylene glycol (PEG), or gelatin, and macroencapsulation devices (>1 mm), capable of containing larger amounts of cells, have arisen as viable approaches to evading the immune system 29,30 . The requirements for these encapsulation modalities are generally (a) that they are biostable within the given implantation site, (b) that they permit sufficient nutrient flow into the capsule as well as release of secreted molecules out of the capsule, and (c) that they do not induce a foreign body response and fibrotic encapsulation.…”

<p>Multifunctional Islet Transplantation Hydrogel Encapsulating A20 High-Expressing Islets</p>

“…1,2 T1D mostly affects young people and is an increasing health issue with an estimated prevalence ranged between 5% and 15% of the total cases of diabetes mellitus worldwide. 3 Currently, life-long administration of exogenous insulin on daily is the primary treatment for T1D to maintain blood glucose close to the normal range and to reduce complications associated with the disease. 4 However, insulin replacement therapy for patients with T1D cannot restore normal glucose homeostasis and leads to a high risk of secondary complications.…”

Co-Microencapsulation of Islets and MSC CellSaics, Mosaic-Like Aggregates of MSCs and Recombinant Peptide Pieces, and Therapeutic Effects of Their Subcutaneous Transplantation on Diabetes

“…This immuno-isolation template could potentially prevent allogeneic or xenobiotic rejections, which would reduce the use of immunosuppressive agents. Over and above that, this strategy might even solve the problem of the donor pancreas shortage by enabling the transplantation of heterologous islets and insulin-secreting cells [6].…”