# Derivation of pancreatic islet-like organoids from human gastric stem cells

> **NIH NIH R01** · WEILL MEDICAL COLL OF CORNELL UNIV · 2024 · $552,366

## Abstract

PROJECT SUMMARY
Islet transplantation offers a potential cure for Type 1 diabetes (T1D). Wide adoption of this promising
therapy requires abundant islet supplies and effective immune protection. My laboratory and others
showed that it was feasible to derive insulin-secreting cells from gastrointestinal (GI) tissues.
However, it has not been possible to mass-produce islet-like organoids from human GI tissues for
detailed assessment of their translational potential.
In preliminary studies, we established methods to culture human gastric stem cells (hGSCs) from
biopsy or autopsy samples that can be expanded to billions. We developed a scalable 2-step method
to produce thousands of GINS (Gastric Insulin Secreting) organoids by transient activation of NGN3
and stable expression of PDX1 and MAFA (collectively referred to as NPM factors). GINS organoids
acquired glucose-stimulated-insulin-secretion (GSIS) within 10 days, and upon transplantation,
rapidly reversed diabetes in mice and maintained normoglycemia for over 3 months, with no tumor
formation. Human GINS organoids thus have favorable attributes as a potential cell product for T1D
treatment.
GINS organoids contain 25% of cells that closely resemble pancreatic β-cells but a paucity of GCG+
and SST+ cells. Human islets have 50-75% β-cells, 25-35% α-cells, and 5% δ-cells. Both α- and δ-
cells exert paracrine effects on β-cell section. In this project, we aim to develop new clonal hGSC
lines and novel nanoparticle-based mRNA transduction method suitable for mass production of
organoids that closely mimic human islets in cell composition and function. These studies are based
on preliminary data indicating that hGSC clonal lines are markedly different, with some predominantly
producing β-like or α-/δ-like cells. Their differentiated progenies can thus be combined to yield islet-
like organoids. We will further study the clonal lines for chromatin features and PDX1/MAFA genomic
binding to gain mechanistic insight in GINS formation. Together, these studies constitute a major step
in advancing the long-term goal of developing GINS organoids for T1D treatment.

## Key facts

- **NIH application ID:** 10897213
- **Project number:** 5R01DK133332-03
- **Recipient organization:** WEILL MEDICAL COLL OF CORNELL UNIV
- **Principal Investigator:** Shahin Rafii
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $552,366
- **Award type:** 5
- **Project period:** 2022-08-24 → 2026-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10897213

## Citation

> US National Institutes of Health, RePORTER application 10897213, Derivation of pancreatic islet-like organoids from human gastric stem cells (5R01DK133332-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10897213. Licensed CC0.

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