# A microwell perfusion plate for manufacturing and testing Islet-like clusters.

> **NIH NIH R03** · WAKE FOREST UNIVERSITY HEALTH SCIENCES · 2024 · $153,713

## Abstract

Abstract/Project Summary
Replacement of insulin-producing cells through islet transplantation in patients with type-1 diabetes (T1D) has
proven to be an effective therapy, resulting in improved metabolic control and quality of life, and in prevention of
long-term T1D complications. To obtain inexhaustible sources of insulin-producing cells, extensive efforts have
been directed towards generating functional β cells or islet-like clusters (ILCs) from human induced pluripotent
stem cells (hIPSC). However, a major barrier in generating ILCs is the considerably low yield of the stem cell
differentiation process and the inability to obtain and maintain mature β cells in long-term culture. These current
shortcomings in traditional culture systems motivate the development of an innovative bioengineered
physiomimetic pancreatic niche. To engineer a physiologically relevant microenvironment for long-term culture
of functional ILCs, we have developed an innovative approach combining three critical components: 1) the use
of a through-pore microwell array to produce homogenously sized ILCs and prevent their agglomeration, 2) the
incorporation of gravitational flow-based perfusion (direct/perpendicular medium flow through ILCs) to allow for
removal of debris, continuous medium exchange, and provide mechanical cues, and 3) the inclusion of human
pancreatic decellularized extracellular matrix (dECM) to ILC to provide more physiologically relevant biochemical
cues. We propose to develop and test an open, long-term culture system for ILCs that provides robust control
on the spatial, biophysical and biochemical culture microenvironment and allows for acquisition of multiple
functional ILC readouts that will help optimizing those critical factors that promote the maturation and functionality
of ILCs from hIPSC-derived endocrine progenitor (EN) cells. A single platform for manufacturing ILCs that
incorporates these three technologies to promote differentiation, maturation, maintenance and testing of ILCs is
not available. Here, we will conduct proof of concept experiments that will advance the field of islet biology and
will validate an innovative platform to produce ILCs for beta cell replacement therapy in T1D. We envision that
our platform can also be adopted for the long-term culture of human islets and for promoting maturation of
neonatal porcine islets.

## Key facts

- **NIH application ID:** 10835931
- **Project number:** 5R03DK135460-02
- **Recipient organization:** WAKE FOREST UNIVERSITY HEALTH SCIENCES
- **Principal Investigator:** Amish Asthana
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $153,713
- **Award type:** 5
- **Project period:** 2023-05-05 → 2026-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10835931

## Citation

> US National Institutes of Health, RePORTER application 10835931, A microwell perfusion plate for manufacturing and testing Islet-like clusters. (5R03DK135460-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10835931. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*