# Studying the Role of the Microenvironment on Differentiation and Maturation of Beta Cells

> **NIH NIH R01** · WASHINGTON UNIVERSITY · 2024 · $462,560

## Abstract

PROJECT SUMMARY
Human pluripotent stem cells (hPSCs) are a promising renewable source of differentiated insulin-producing
islets for diabetes cell replacement therapy. Within the islets of diabetic patients, beta cells are dead or dys-
functional, causing loss of blood glucose control. There is no cure for diabetes, and current treatments are
insufficient in controlling the disease for many patients. Transplantation of insulin-secreting cells could be an
effective treatment for diabetes, and a small number of patients have been implanted with cadaveric donor
islets, remaining insulin independent for years. Unfortunately, many factors limit this approach, particularly the
scarcity and variability of isolated human islets, with patients often requiring islets from multiple donors to
achieve normal blood sugar. The lack of mature replacement tissues is a critical barrier to cellular therapy. We
have previously published a strategy for the scalable generation of hPSC-derived islets (SC-islets) in vitro that
are capable of secreting insulin and restoring normoglycemia in diabetic mice. However, a current challenge
with these in vitro-derived cells is the incomplete and uncontrolled differentiation to fully mature SC-islets that
are equal to primary cells. Our goal is to understand how modulating the microenvironment affects hPSC cell
fate decisions to and the subsequent maturation of SC-islets and to use this to innovate SC-islet generation
strategies for use in cellular therapy. To this end, we will study patterning of definitive endoderm and other
intermediate cell types produced by microenvironmental perturbation. Subsequent generation of the SC-islets
will be investigated, including characterizing in vitro and in vivo function and marker expression. The outcome
of this proposal will have a positive impact by filling gaps in our understanding of what controls SC-islet cell
fate specification to individual cell types, as well as how these cells mature. Successful completion of our
studies will inform strategies to improve SC-islet differentiation protocols for diabetes cell replacement therapy
and disease modeling.

## Key facts

- **NIH application ID:** 10871835
- **Project number:** 5R01DK114233-07
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** Jeffrey Robert Millman
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $462,560
- **Award type:** 5
- **Project period:** 2017-07-01 → 2027-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10871835

## Citation

> US National Institutes of Health, RePORTER application 10871835, Studying the Role of the Microenvironment on Differentiation and Maturation of Beta Cells (5R01DK114233-07). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10871835. Licensed CC0.

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