# Engineering human islet-like organoids for transplantation

> **NIH NIH R01** · SALK INSTITUTE FOR BIOLOGICAL STUDIES · 2020 · $865,040

## Abstract

ABSTRACT
 Pancreatic islet transplantation offers long-term treatment for Type 1 diabetes, however the shortage of
donors and the need for immunosuppressive drugs restrict its therapeutic utility. Islet-like organoids generated
from human pluripotent stem cells (PSCs) are an attractive alternative. Moreover, given the increasing
appreciation for the role of multi-cellular organization in the functional maturation and maintenance of organs,
islet-like organoids have the potential for superior functionality compared to β cells alone. The goal of this
project is to develop the next generation of human islet-like organoids (HILOs) from stem cells for efficient and
immune evasive transplantation. The underlying hypothesis is that a combination of a novel 3D differentiation
protocol, modulation of cell surface signaling, and anti-inflammation transcriptional machinery will enable
HILOs to survive long-term and function in an immune competent environment in vivo. To achieve this goal,
Aim 1 proposes to establish the long-term efficacy and safety profile of HILOs, of which the function has been
validated extensively in vitro. Aim 2 proposes to develop immune-tolerant HILOs by engineering the expression
of PD-L1 and demonstrating the efficacy in humanized immune-competent diabetic mice. To further extend
protection of transplanted HILOs, Aim 3 proposes to apply pharmacological activation of vitamin D signaling to
alleviate cytokine stress on transplanted HILOs. The goal is to determine whether the incorporation of these
strategies to improve survival as well as minimize allo-rejection of transplanted HILOs will result in an unlimited
supply of therapeutically viable engineered islets for treating diabetes.

## Key facts

- **NIH application ID:** 9970225
- **Project number:** 5R01DK120480-03
- **Recipient organization:** SALK INSTITUTE FOR BIOLOGICAL STUDIES
- **Principal Investigator:** RONALD M EVANS
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $865,040
- **Award type:** 5
- **Project period:** 2018-09-30 → 2022-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9970225

## Citation

> US National Institutes of Health, RePORTER application 9970225, Engineering human islet-like organoids for transplantation (5R01DK120480-03). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/9970225. Licensed CC0.

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