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This research investigates how allogeneic neo-islets confer durable glycemic control in diabetic NOD mice compared to traditional islet transplants.

June 10, 2026

1314-OR: Allogeneic Islets Are Rejected by Diabetic NOD Mice while Allogeneic Neo-Islets, 3D Organoids of Islet and Mesenchymal Stromal Cells, Durably Cure Their Type 1 Diabetes without Antirejection Drugs: Mechanisms

Key Points

This research investigates how allogeneic neo-islets confer durable glycemic control in diabetic NOD mice compared to traditional islet transplants.
Diabetic female NOD mice (~12 weeks, Blood Glucose > 350 mg/dL) received three different treatments: allo neo-islets, allo islets, and vehicle.
Blood glucose levels, body weights, and survival were monitored over 11 weeks, alongside immune response assessments.
Insulin and C-Peptide expressions, as well as autoreactive T cell and regulatory T cell populations, were analyzed.
NI therapy achieved normalized blood glucose levels in treated mice, while allogeneic islet and vehicle groups became hyperglycemic and exhibited mortality.
NI engraftment led to insulin and C-Peptide expression, reduced T helper cells, and increased regulatory T cells in treated mice.
Minimal renal fibrosis was observed in NI-treated group compared to significant fibrosis in islet-treated mice.

Abstract

Introduction and Objective: T1D 350 mg/dL) were treated i.p. in 3 Groups (Grp; n=6 each). 1: allo (C57/Bl6) NIs; 2: allo, C57/Bl6 islets; 3: vehicle. Prior to therapies (all grps), BG levels were controlled with insulin pellets. Monitoring in each group: BG levels (tail vein); body weights; survival. At 11 weeks, omental NI engraftment, insulin autoreactive T cell IgG levels against allo NIs renal fibrosis. Results: NI therapy normalized blood glucose levels in Grp 1, improved renal function and body weights. Grps 2 and 3 became hyperglycemic Grp 1 sera showed none. Kidney trichrome stains from Grp 1 showed minimal interstitial fibrosis vs Grp 2. Conclusion: Allo NI therapy of NOD mice achieves durable euglycemia and renoprotection. Identical 3 yr observations are found in in allo-NI treated diabetic dogs. Human clinical studies are planned. Disclosure C.M. Westenfelder: Board Member; Current; SymbioCellTech, LLC. A. Gooch: Board Member; Current; SymbioCellTech, LLC. Employee; Current; SymbioCellTech, LLC.

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