# Evaluation of a beta cell replacement therapy combined product that avoids the need for immunosuppression via localized induction of immune tolerance

> **NIH NIH R41** · REGENERATIVE MEDICAL SOLUTIONS, INC. · 2022 · $274,984

## Abstract

Project Summary/Abstract
Diabetes is an increasingly important health problem worldwide. Despite recent advances in diabetes care,
including long-acting insulin formulations, insulin pumps, and continuous glucose monitors, a majority of diabetic
patients cannot achieve currently recommended targets for blood glucose control. Although transplantation of
diabetic patients with donor-derived pancreatic islets or intact pancreas effectively restores blood glucose
control, such procedures remain rare due to limited source material and the requirement for life-long
immunosuppression. To circumvent the first of these obstacles, Regenerative Medical Solutions (RMS) has
developed a proprietary protocol for converting induced pluripotent stem cells (iPSC), a virtually unlimited cell
source, into islet-like clusters (ILC) of cells that include insulin-producing beta-like cells. To eliminate the need
for immunosuppression, iTolerance, Inc, has advanced a product consisting of Fas ligand conjugated
microparticles (iTOL-100) that, when co-transplanted with rodent or primate islets, create localized immune
tolerance and provide long-term protection from allograft rejection in animal models of diabetes. In this proposed
project, RMS will work with the Diabetes Research Institute at the University of Miami to test a combined product
consisting of ILC mixed with iTOL-100 as a candidate cell-based diabetes therapeutic that will alleviate the need
for life-long immunosuppression. To establish the feasibility of such a combined product, we will first demonstrate
in vitro cytocompatibility of the two products (ILC and iTOL-100). Next, the in vivo cytocompatibility and
therapeutic efficacy of the combined product will be verified in an immunocompromised mouse model of
diabetes. Finally, the ability of the combined product to delay the xenograft rejection response in immune
competent diabetic mice will be determined. Together, these studies will lay the groundwork for a Phase II project
in which the combined product will be tested for its ability to evade allograft rejection in mice reconstituted with
a human immune system, along with other essential studies that will enable clinical translation. The availability
of an abundant beta cell-replacement therapy that does not require chronic immunosuppressive medication for
long-term allograft tolerance will extend the reach of this form of treatment to the ever-growing numbers of
patients who may benefit from it.

## Key facts

- **NIH application ID:** 10603016
- **Project number:** 1R41DK135191-01
- **Recipient organization:** REGENERATIVE MEDICAL SOLUTIONS, INC.
- **Principal Investigator:** DENA E COHEN
- **Activity code:** R41 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $274,984
- **Award type:** 1
- **Project period:** 2022-09-23 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10603016

## Citation

> US National Institutes of Health, RePORTER application 10603016, Evaluation of a beta cell replacement therapy combined product that avoids the need for immunosuppression via localized induction of immune tolerance (1R41DK135191-01). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/10603016. Licensed CC0.

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