Conformal Coating of Stem Cell-Derived Islets for β Cell Replacement in Type 1 Diabetes

Abstract

The scarcity of donors and need for immunosuppression limit pancreatic islet transplantation to a few patients with labile type 1 diabetes. Transplantation of encapsulated stem cell-derived islets (SC islets) might extend the applicability of islet transplantation to a larger cohort of patients. Transplantation of conformal-coated islets into a confined well-vascularized site allows long-term diabetes reversal in fully MHC-mismatched diabetic mice without immunosuppression. Here, we demonstrated that human SC islets reaggregated from cryopreserved cells display glucose-stimulated insulin secretion in vitro. Importantly, we showed that conformally coated SC islets displayed comparable in vitro function with unencapsulated SC islets, with conformal coating permitting physiological insulin secretion. Transplantation of SC islets into the gonadal fat pad of diabetic NOD-scid mice revealed that both unencapsulated and conformal-coated SC islets could reverse diabetes and maintain human-level euglycemia for more than 80 days. Overall, these results provide support for further evaluation of safety and efficacy of conformal-coated SC islets in larger species.

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

“…Therefore, we thought that the amount of anti-inflammatory cytokines secreted from MSC CellSaics was not sufficient for suppression of the immune response to ALG-PLO microcapsules [26,34]. As future work, we would like to study about a method to increase the amount of anti-inflammatory cytokines from MSC CellSaics [35], or use of microcapsules with high biocompatibility [11,[26][27][28] in order to improve %NBGL.…”

“…To provide a feasible immuno-isolated environment for islets, there are three requirements, based on the literature [4][5][6]9,21]: (1) the ability to block humoral and cellular immunity; (2) allowing the permeation of small molecules such as insulin and glucose; (3) physical resistance that does not break at the transplantation site. The microencapsulation of islets has been shown to meet these requirements, and many techniques have been reported [7,11,[21][22][23][24][25][26][27][28]. As a microencapsulating material for establishing immuno-isolated environments, alginate polymer is often used because it is inexpensive, biocompatible, and can create a gel easily at room temperature in aqueous solution with divalent ions.…”

New trends in cellular therapy

“…These hESC-derived islet cells were found to be capable of functional insulin secretion upon exposure to high-glucose or high-potassium stimuli (Vegas et al, 2016). Furthermore, both companies have demonstrated rescue of T1D animal models (such as rodents and larger animals) with these cells (Vegas et al, 2016;Schulz, 2015) and have developed immune-protected encapsulated islet/β-cells by immobilizing cells within semi-permeable membrane polymer shells that can provide mechanical protection and immuno-isolation (Vegas et al, 2016;Stock et al, 2020). Such encapsulated islets/ β-cells can release insulin to the extracellular space in response to physiological and pharmacological stimuli such as high glucose, high K + conditions, amino acids and others (Vegas et al, 2016).…”

Diabetes Mellitus Is a Chronic Disease that Can Benefit from Therapy with Induced Pluripotent Stem Cells

“…Multiple preclinical studies in β-cell generation have been developed to date and, most of them have been focused on type 1 DM where the β-cells obtained have been derived from both healthy and diabetic individuals [ 188 , 189 , 190 ]. Millman et al [ 191 ], demonstrated that there was no difference between β-cells obtained from diabetic and non-diabetic patients in order to transplant β-cells into type 1 diabetic patients.…”