# Scaffolds for culture and transplantation of islet organoids

> **NIH NIH R01** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2022 · $550,689

## Abstract

Allogeneic islets transplanted into the liver have shown promise clinically for treatment of Type 1 Diabetes
(T1D), yet their supply is limited. These limitations have led to the investigation of human pluripotent stem cells
(hPSC) as an unlimited source of functional β-cells. Multiple investigators have demonstrated the feasibility of
differentiating hPSC to immature β-cells in vitro and successfully transplanted these cells into rodents which
allowed further maturation into glucose-responsive insulin-producing β-cells. The main challenges of deriving
β-cells in vitro from hPSCs for transplantation are i) the efficiency and consistency of the hPSC differentiation,
and ii) previous transplants are typically performed at non-translatable sites, and the adaptation to clinically
translatable sites adds additional inefficiencies. Herein, we propose an innovative strategy of culturing the
hPSCs on microporous polymer scaffolds as a platform to obtain efficient differentiation of hPSCs to islet
organoids in vitro, which contain multiple endocrine cell types that are found within an islet. Furthermore, the
organoids can be directly transplanted on scaffolds at a clinically relevant site, namely the peritoneal fat,
without disrupting the niche that develops within the pores. PI Dr. Shea has developed the scaffolds for the
transplantation of primary islets into mice at a clinically translatable site that allows for efficient engraftment and
function, and the reversal of hyperglycemia with a minimal islet mass. co-PI Dr. Spence is a developmental
biologist with expertise in organoid culture that is collaborating on the scaffold design and analysis of in vivo
maturation. Aim 1 will test the hypothesis that the differentiation of hPSC-derived pancreatic progenitors on 3D
microporous scaffolds can increase the efficiency for forming islet organoids in vitro. Scaffolds will be created
with controlled architecture and modified with extracellular matrix (ECM) proteins to facilitate organization and
differentiation of cells into islet structures. The maturity of the organoids and cellular subpopulations will be
monitored through flow cytometry, gene expression of pancreatic makers, the activity of key transcription
factors, and insulin secretion. Established conditions for differentiating hPSC to β-cells will be used as a
control. Aim 2 will investigate the in vivo maturation and function following transplantation of scaffolds with islet
organoids in the pores. We will investigate the survival and maturation of the organoids upon transplantation
into the peritoneal fat, considered a translatable site, and observe the restoration of euglycemia in diabetic
mouse models. Dr. Jan Stegemann will consult on vascularization of the graft. In collaboration with a leading
islet biologist, Dr. Peter Arvan, we will assess the function of the transplanted islet organoids relative to that of
native islets, and analyze the cells by flow cytometry and gene expression for relevan...

## Key facts

- **NIH application ID:** 10380872
- **Project number:** 5R01DK121462-03
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **Principal Investigator:** Lonnie D Shea
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $550,689
- **Award type:** 5
- **Project period:** 2020-07-01 → 2024-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10380872

## Citation

> US National Institutes of Health, RePORTER application 10380872, Scaffolds for culture and transplantation of islet organoids (5R01DK121462-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10380872. Licensed CC0.

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