ArticleTransplantation direct2026
In Vitro Evaluation of Necrostatin-1 Microparticles for Limiting Stress-induced Cell Death and Preserving Islet Function.
Article in Transplantation direct, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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7 authors.
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Abstract
Background: Islet transplantation offers a promising therapy for type 1 diabetes, but early β-cell loss due to stress-induced cell death limits graft survival and function. Although apoptosis has been extensively studied, necroptosis, a regulated form of necrotic cell death, remains an underexplored contributor to β-cell dysfunction. Herein, we evaluated sustained necrostatin-1 (Nec-1) delivery via poly(lactic-co-glycolic acid) (PLGA) microparticles (MPs) to protect islets from stress-induced damage in vitro. Methods: Nec-1-loaded PLGA MPs were synthesized by single-emulsion solvent evaporation and characterized by scanning electron microscopy and high-performance liquid chromatography for size, morphology, and drug encapsulation. Mouse islets were coincubated with Nec-1 or empty MPs for 24 h, followed by induction of endoplasmic reticulum stress with thapsigargin. Glucose-stimulated insulin secretion and cytokine release were quantified to assess β-cell function and inflammatory response. Results: Nec-1 MPs were spherical with a median diameter of 10.34 μm (interquartile range [IQR], 6.55-15.17 μm) and an encapsulation efficiency of 36.2% (IQR, 31.1%-40.0%). Release studies demonstrated an initial burst of 24.8% (IQR, 21.8%-30.3%) by day 3, followed by sustained delivery up to 53.6% (IQR, 52.3%-57.4%) by day 14, with minimal impact on media pH. Under thapsigargin-induced stress, Nec-1 MP-treated mouse islets maintained glucose-stimulated insulin secretion, with insulin release increasing from 2.63% (IQR, 1.42%-5.74%) to 8.63% (IQR, 7.97%-14.42%, Conclusions: Nec-1-loaded PLGA MPs provide sustained, localized protection of β-cells from necroptotic and inflammatory stress in vitro. Given the sustained and targeted drug delivery, these findings provide a foundation for future in vivo translation to provide graft-localized therapeutic intervention and improve islet survival, engraftment, and long-term function.
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