In Vitro Development and Evaluation of an Endovascular Islet Cell Stent for Type 1 Diabetes Mellitus.

Abstract

Purpose: To describe the in vitro development and benchtop evaluation of the IsletStent, an endovascular biologic stent-graft incorporating expanded polytetrafluoroethylene (ePTFE) semipermeable membranes, designed for portal venous delivery of pancreatic islets as a treatment for type 1 diabetes mellitus.

Materials and methods: Prototypes with a 0.22 μm pore ePTFE membrane were seeded with murine (approximately 5,000-6,000 islet equivalents [IEQ]) or human (approximately 10,000 IEQ) islets. A benchtop normothermic perfusion circuit simulated intravascular deployment. Glucose-stimulated insulin secretion (GSIS) was assessed in a repeated-measures design (n = 4 devices per experiment); murine islet-seeded devices were perfused under zero (0 mM), low (2.8 mM), and high (28 mM) glucose, and human islet-seeded devices under low and high glucose only, with insulin quantified by ELISA. Computational fluid dynamics (CFD) modeling under idealized, non-physiologic single-fluid conditions evaluated candidate device geometries.

Results: Murine islet-seeded devices demonstrated glucose-responsive insulin secretion: 3-hour insulin concentrations were 83 ± 8 vs. 145 ± 20 μIU/mL under low vs. high glucose (p = 0.02), and secretion rates were 5,344 ± 144 vs. 6,795 ± 503 μIU/hr (p = 0.008). Human islet-seeded devices responded concordantly, with 3-hour insulin concentrations of 229 ± 13 vs. 300 ± 17 μIU/mL (p = 0.014).

Conclusion: In this benchtop perfusion model, islets housed within an ePTFE-based endovascular stent-graft retained glucose-responsive insulin secretion. In vivo evaluation of islet viability, direct immunoisolation, hemodynamic impact, and long-term function is required before clinical translation.