Islet Encapsulation: New Developments for the Treatment of Type 1 Diabetes

Abstract

Islet transplantation is a promising approach for the treatment of type 1 diabetes (T1D). Currently, clinical islet transplantation is limited by allo - and autoimmunity that may cause partial or complete loss of islet function within a short period of time, and long-term immunosuppression is required to prevent rejection. Encapsulation into semipermeable biomaterials provides a strategy that allows nutrients, oxygen and secreted hormones to diffuse through the membrane while blocking immune cells and the like out of the capsule, allowing long-term graft survival and avoiding long-term use of immunosuppression. In recent years, a variety of engineering strategies have been developed to improve the composition and properties of encapsulation materials and to explore the clinical practicality of islet cell transplantation from different sources. In particular, the encapsulation of porcine islet and the co-encapsulation of islet cells with other by-standing cells or active ingredients for promoting long-term functionality, attracted significant research efforts. Hydrogels have been widely used for cell encapsulation as well as other therapeutic applications including tissue engineering, cell carriers or drug delivery. Here, we review the current status of various hydrogel biomaterials, natural and synthetic, with particular focus on islet transplantation applications. Natural hydrophilic polymers include polysaccharides (starch, cellulose, alginic acid, hyaluronic acid, chitosan) and peptides (collagen, poly-L-lysine, poly-L-glutamic acid). Synthetic hydrophilic polymers include alcohol, acrylic acid and their derivatives [poly (acrylic acid), poly (methacrylic acid), poly(acrylamide)]. By understanding the advantages and disadvantages of materials from different sources and types, appropriate materials and encapsuling methods can be designed and selected as needed to improve the efficacy and duration of islet. Islet capsule transplantation is emerging as a promising future treatment for T1D.

Cryopreservation of Cell Sheets for Regenerative Therapy: Application of Vitrified Hydrogel Membranes

“…In other medical applications, alginate is used in fibrous gels (surgical threads), alginate salts (wound dressings), drug delivery, and tissue engineering [ 66 ]. Islet transplantation is an effective therapeutic modality to stabilize glycemic control in type 1 diabetes patients [ 67 ]. Islet encapsulation in an alginate hydrogel can immunosuppress, and maintain long-term patient survival.…”

Replenishable prevascularized cell encapsulation devices increase graft survival and function in the subcutaneous space

“…Encapsulation devices offer a physical barrier to protect transplanted beta cells from immune attack; however, this barrier can limit the diffusion of oxygen and nutrients, causing ischemic stress detrimental to graft survival. This ischemic stress varies based on the transplantation site of the device 1,2,4,7–10,14,15 …”

“…While these strategies may improve blood vessel formation, these methods require at least 10 days to create a dense vascular network that is well integrated with the host vasculature after cells have already been implanted in the subcutaneous space. Due to this limitation, these methods cannot rescue most of the graft loss that occurs within the initial days of implantation 7,11,12,15,21,38 …”

“…This ischemic stress varies based on the transplantation site of the device. 1,2,4,[7][8][9][10]14,15 An ideal transplantation site for cell encapsulation devices includes (1) a dense vascular network that allows for insulin and glucose exchange, along with high oxygen and nutrient supply to the graft; (2) a hospitable microenvironment that prevents initial loss of cells posttransplant; (3) a minimally invasive procedure for implanting, monitoring, and retrieving the graft. Transplantation in the subcutaneous space allows for minimally invasive implantation and retrieval.…”

“…Due to this limitation, these methods cannot rescue most of the graft loss that occurs within the initial days of implantation. 7,11,12,15,21,38 Another promising strategy to improve islet vascularization is the prevascularization of encapsulation devices at the transplantation site.…”