Engineering Strategies to Improve Islet Transplantation for Type 1 Diabetes Therapy

Abstract

Type 1 diabetes is an autoimmune disease in which the immune system attacks insulin-producing beta cells of pancreatic islets. Type 1 diabetes can be treated with islet transplantation; however, patients must be administered immunosuppressants to prevent immune rejection of the transplanted islets if they are not autologous or not engineered with immune protection/isolation. To overcome biological barriers of islet transplantation, encapsulation strategies have been developed and robustly investigated. While islet encapsulation can prevent the need for immunosuppressants, these approaches have not shown much success in clinical trials due to a lack of long-term insulin production. Multiple engineering strategies have been used to improve encapsulation and post-transplantation islet survival. In addition, more efficient islet cryopreservation methods have been designed to facilitate the scaling-up of islet transplantation. Other islet sources have been identified including porcine islets and stem cell-derived islet-like aggregates. Overall, islet-laden capsule transplantation has greatly improved over the past 30 years and is moving toward becoming a clinically feasible treatment for type 1 diabetes.

Deep Learning‐Enabled Label‐Free On‐Chip Detection and Selective Extraction of Cell Aggregate‐Laden Hydrogel Microcapsules

“…If no cell aggregateladen microcapsule is detected, DEP stays off and the microcapsule continues to flow down the oil channel (Figure 3a. [7][8][9]. This selective extraction process can be seen in both Video S1 (Supporting Information, in full speed) and Video S2 (Supporting Information, in full speed with one exception: when extraction occurs, it is slowed down to 10% speed for better visualization of the extraction process).…”

“…[1][2][3][4][5] For example, microcapsules can be used to create a biomimetic environment for ovarian follicles and a biocompatible immunogenic barrier for stem cell and islet transplantation. [1][2][3][4][5][6][7][8][9][10] Microfluidics has been widely explored for cell and tissue encapsulation because of its good controllability in terms of the size, morphology, and composition of the resultant microcapsules. [11,12] Microfluidic cell encapsulation is usually accomplished by shearing cell-laden aqueous fluids with a water-immiscible fluid (e.g., oil).…”

“…[7,[16][17][18][19][20][21] This large number of empty microcapsules make downstream processing difficult, and in particular, are undesired for cell/tissue transplantation for which the space available in vivo for housing the transplants is very limited. [9,22] To remove empty microcapsules, sorting is needed. This can be done manually or by moving all the microcapsules to another device for sorting, which is tedious and may cause sample loss, contamination, and/or cell damage.…”

Engineering Islets From Stem Cells: The Optimal Solution for the Treatment of Diabetes?

“…Although a significant progress has been achieved for the development of islet clusters from human stem cells, only a few practical applications of bioengineering technology are realized in the treatment of diabetes. For the treatment of T1DM, novel attempts have focused on the development of bioengineering strategies such as microencapsulation with the aim to avoid immunosuppressive agents ( 170 ). For the treatment of T2DM, the exploration for new treatments includes stem cell differentiation, drug therapy and other methods ( 171 ).…”

Versatile surface modification of millimeter‐scale “aqueous pearls” with nanoparticles via self‐polymerization of dopamine

“…They play a vital role in protecting the susceptible materials, shielding odor, and controlling the release of active compounds 1,2 . Compared with nano/microcapsules, the millimeter‐scale capsules not only own high capacity and good stability but also appear monodisperse and high sphericity, which have been applied in many specific fields, such as microreactor, 3 catalysis, 4 high energy density physics research, 5,6 water treatment, 7 cells cultivation system, drug delivery, and enzyme immobilization 8‐11 . For example, cells were entrapped within liquid‐core surrounded by a thin gel membrane of millimeter capsules in the cells cultivation system 12 .…”