Long-Term Function of Islets Encapsulated in a Redesigned Alginate Microcapsule Construct in Omentum Pouches of Immune-Competent Diabetic Rats

Abstract

Objectives Our study aim was to determine encapsulated islet graft viability in an omentum pouch and the effect of FGF-1 released from our redesigned alginate microcapsules on the function of the graft. Methods Isolated rat islets were encapsulated in an inner core made with 1.5% low-viscosity high-mannuronic acid (LVM) alginate followed by an external layer made with 1.25% low-viscosity high-guluronic acid (LVG) alginate with or without FGF-1, in microcapsules measuring 300 – 400 μm in diameter. The two alginate layers were separated by a perm-selective membrane made with 0.1 % Poly-L-Ornithine (PLO), and the inner LVM core was partially chelated using 55 mM sodium citrate for 2 min. Results A marginal mass of encapsulated islet allografts (~2000 islets/kg) in Streptozotocin-diabetic Lewis rats caused significant reduction in blood glucose levels similar to the effect observed with encapsulated islet isografts. Transplantation of allo-islets co-encapsulated with FGF-1 did not result in better glycemic control, but induced greater body weight maintenance in transplant recipients compared to those that received only allo-islets. Histological examination of the retrieved tissue demonstrated morphologically and functionally intact islets in the microcapsules, with no signs of fibrosis. Conclusion We conclude that the omentum is a viable site for encapsulated islet transplantation.

Stimulation of vascularization of a subcutaneous scaffold applicable for pancreatic islet‐transplantation enhances immediate post‐transplant islet graft function but not long‐term normoglycemia

“…The 0.5 μg aFGF group received a 100 μL aFGF‐loaded liposome injection and the 1.0 μg aFGF group received 200 μL aFGF loaded liposomes. The concentrations were chosen because 0.5 μg aFGF was most effective in enhancing the tube formation and in previous studies concentrations of 0.5–1.0 μg aFGF showed to improve islet engraftment 36, 37. Efficacy of the 800 islet‐dose in sham‐injected scaffolds was compared with that of scaffold treated with liposomes containing either 0.5 or 1.0 μg aFGF.…”

Encapsulation technologies in beta cell replacement therapies for Type 1 diabetes

“…Recently, Shahjalal et al and Kudva et al reported successful differentiation of human-derived iPSCs into insulin--producing cells without using xenogeneic products or viral transgenic vectors respectively [168]. However, Thatava et al suggested that translation of results observed in mice might face significant challenges before translation to humans when he reported that iPSCs isolated from T1D patients exhibited significant variations in their ability to differentiate into insulin-expressing islet-like cells [169]. …”

“…Pancreatic stem cells [160,161], hESCs [162][163][164], induced pluripotent stem cells (iPSCs) [165][166][167][168][169], mesenchymal [170][171][172][173][174] and adipose-derived stem cells (ADSCs) [175,176] have all been used to derive islet-like cell clusters or insulin-producing cells (IPCs) that are viable, express markers similar to terminally differentiated β-cells (Insulin, GLUT2) and are able to respond to a glucose challenge. These cells have all demonstrated good function after encapsulation within bioencapsulation devices and several in vivo studies have also been conducted.…”

Imaging of Hydrogel Microsphere Structure and Foreign Body Response Based on Endogenous X-Ray Phase Contrast

“…28 Low-viscosity high-mannuronic acid (LVM) alginate (20-200 mPas; Nova-Matrix, Sandvika, Norway) was dissolved in 1.5% Eagle's minimum essential medium (MEM; Sigma-Aldrich, St. Louis, MO). Poly-l-ornithine (PLO; 30-70 kDa, Sigma-Aldrich), sodium citrate (Sigma-Aldrich), ultrapurified low-viscosity high-guluronic acid (LVG) alginate (75-200 kDa, G/M ratio £1), and LVM alginate (75-200 kDa, G/M ratio ‡1.5; Nova-Matrix, Sandvika, Norway) were also prepared in MEM.…”

“…4,9,24 Histological and immunohistochemical methods are also frequently used but are invasive and destructive, do not allow for three dimensional (3D) assessment of the sample, often alter biomaterial structure, and require processing and staining techniques. 4,[24][25][26][27][28][29] There is a need for noninvasive imaging that allows for 3D assessment of the implanted grafts and local tissue response to monitor and predict long-term success of the transplant. The ideal imaging technique would not require exogenous contrast and be nondestructive.…”