A composite capsule strategy to support longevity of microencapsulated pancreatic β cells

Pancreatic stellate cells support human pancreatic β-cell viability in vitro and enhance survival of immunoisolated human islets exposed to cytokines

“…Next, we investigates whether the PSCs provide benefits for islets in alginate microcapsules, as these islets suffer from cytokine stress post-transplantation, which is associated with up to 60 % loss of the islet tissue in the first two weeks after implantation [ 7 , 29 ]. We tested the impact of HPSCs in conventional alginate capsules [ 12 , 30 ], as well as in recently developed composite capsules containing the immunomodulatory molecule pectin and ECM components (collagen type IV and RGD) with necrostatin-1 (Nec-1), as well as amino acids (alanine, glutamine, glycine) [ 9 , 31 ]. To test the impact of HPSCs in these capsules, we compared the following groups ( Fig.…”

“…To test the impact of HPSCs in these capsules, we compared the following groups ( Fig. 4 A): human islets encapsulated in alginate (alg: control group) or a composite group (com) of collagen type IV and RGD with Nec-1and amino acids [ 9 ]. Encapsulated human islets were co-cultured with PSCs (alg/PSC and com/PSC) or alone.…”

“…The pectin with low degree of methyl esterification (DM) had profound influence on the performance of islets in capsules [ 8 , 10 ]. The composite design capsules, with collagen type IV, laminin sequence RGD, Nec-1, and amino acids (alanine, glutamine, glycine) together with DM18 pectin, provide a superior microenvironment for islet transplantation with immunoisolation [ 9 ]. The combination of composite capsules together with co-transplantation with PSCs likely synergistically prolong the life of islet-graft.…”

“…To obtain long-term functioning immunoisolated islet grafts, it is essential to make modifications both on the outside and inside of the capsules [ 7 ]. Examples of modifications on the outside of capsules include the adherence of antifibrotic factors or immunomodulating molecules such as pectins [ 8 , 9 ]. Modifications inside the capsules are especially needed to prevent the loss of islet-cells under cytokine stress.…”

“…This may lead to the loss of up to 60 % of the transplanted islet graft in the immediate period after transplantation [ 7 , 11 ]. We have previously shown that incorporating specific extracellular matrix (ECM) components, such as collagen type IV and RGD (arginine-glycine-aspartic acid), or other survival factors into the intracapsular environment can extend the functional survival of islets [ 9 , 11 , 12 ]. However, more might be needed for long-term survival.…”