# Islet encapsulation to elicit localized immunosuppression and immune modulation following transplantation

> **NIH NIH R01** · UNIVERSITY OF KANSAS MEDICAL CENTER · 2024 · $552,601

## Abstract

Project Summary/Abstract
Type 1 diabetes (T1D) is an autoimmune disease resulting in pancreatic b-cell destruction. Islet-infiltrating
leukocytes will generate reactive oxygen species (ROS), proinflammatory cytokines/chemokines, and T cell
effector molecules involved in b-cell lysis. Islet transplantation is a promising treatment for T1D, but numerous
hurdles including immune-mediated rejection, adverse effects of immunosuppression on islet function, ideal
sites for transplantation, and declining allograft survival impede human translatability. Islet encapsulation may
provide immunoprotection to preserve islet function and prevent immune responses against the islet graft
following transplantation. The goal of this project is to assess the efficacy of a pre-vascularized subcutaneous
device-less (DL) site for transplantation and to enhance a novel cytoprotective coating for islet encapsulation
consisting of a layer-by-layer hydrogen-bonded assembly of tannic acid (TA), an immunomodulatory
antioxidant, poly(N-vinylpyrrolidone) (PVPON), a cytocompatible natural and synthetic polymer, and CTLA-4-Ig
to inhibit T cell activation in mouse models and humanized mouse models of islet allotransplantation.
Transplantation of (PVPON/TA/CTLA-4-Ig)-encapsulated islets in the DL site are functional, does not elicit a
foreign body reaction unlike the microencapsulated devices currently being evaluated in clinical trials, can
decrease proinflammatory immune responses, and delay allograft rejection in the absence of global
immunosuppression. Our overarching hypothesis is that (PVPON/TA/CTLA-4-Ig) encapsulation of islets
can elicit localized immunosuppression and preserve islet function following transplantation into a
pre-vascularized device-less site without stimulated deleterious fibrosis. To address this hypothesis, the
following independent and interrelated aims will be defined in mouse and human samples. (1) Determine if
(PVPON/TA/CTLA-4-Ig) encapsulation can suppress proinflammatory innate and adaptive immune responses
after transplantation. (2) Determine if (PVPON/TA/CTLA-4-Ig) encapsulation stabilizes b-cell function and
decreases inflammation. The insights gained from our studies will identify additional pathways that can be
exploited to conjugate novel inhibitors of proinflammatory immune responses to our adaptable
(PVPON/TA/CTLA-4-Ig) coatings to further delay islet allograft rejection for future human translational studies.

## Key facts

- **NIH application ID:** 10927348
- **Project number:** 5R01DK131716-02
- **Recipient organization:** UNIVERSITY OF KANSAS MEDICAL CENTER
- **Principal Investigator:** Eugenia Kharlampieva
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $552,601
- **Award type:** 5
- **Project period:** 2023-09-15 → 2028-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10927348

## Citation

> US National Institutes of Health, RePORTER application 10927348, Islet encapsulation to elicit localized immunosuppression and immune modulation following transplantation (5R01DK131716-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10927348. Licensed CC0.

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