# Probing the human pancreatic and islet matrisome

> **NIH NIH F31** · UNIVERSITY OF WISCONSIN-MADISON · 2020 · $34,030

## Abstract

PROJECT SUMMARY:
 Human pluripotent stem cells (hPSCs) have the potential to differentiate into any cell type of the body.
Deriving insulin-producing pancreatic beta cells from hPSCs holds great potential as a diabetes treatment. While
recent advances have been made in generating stem cell-derived beta cells (SCBCs), these cells do not fully
recapitulate mature beta cells in vitro, but do become more functionally mature after transplantation. This
suggests that one or more components of the in vivo milieu, such as vascularization, hormone and growth factor
signals, and/or extracellular matrix (ECM) interactions, aid in beta cell maturation. We seek to recapitulate an in
vivo-like niche for terminal differentiation and maturation in vitro with the goal of improving the generation of
functional SCBCs.
 The ECM is a network of proteins and polysaccharides, of a unique composition in each tissue, capable of
guiding cell migration, morphology, function and differentiation. In adult human islets, ECM has been found to
play a key role in cell survival and insulin secretion, while in fetal islets, ECM has also been associated with beta
cell proliferation, migration, and maturation. These data suggest that ECM is important for beta cell and islet
health. During islet isolation from the pancreas, much of the native ECM is destroyed, and the health and function
of these islets is extremely limited in vitro. Moreover, in vitro-derived SCBCs possess scant amounts of ECM.
An unsuitable microenvironment, due to impaired or deficient ECM in vitro, may be a barrier to successful islet
and SCBC culture.
 Our lab is among the first to apply decellularization techniques to the human pancreas and isolate high quality
ECM (hP-ECM). The isolation of hP-ECM and the development of state-of-the art quantitative mass spectrometry
(MS) techniques introduces the ability to more comprehensively study the human pancreatic matrisome, which
ultimately will provide insight to create mimetic constructs. As ECM has been implicated to play an important role
in fetal and adult islets, and our preliminary data show differences in the abundance of some matrix proteins
between fetal and adult samples, I propose in Aim 1 to analyze decelled ECM samples alongside native tissue,
from four distinct age groups: fetal, juvenile (1-18 yrs), young adult (21-29 yrs), and older adult (55+ yrs) using
MS with DiLeu mass tag labeling. To target islet ECM specifically, knowing the isolation process damages islet
ECM, I will use modern MS imaging techniques in Aim 2 to quantitatively and comprehensively measure in situ
human islet-specific ECM composition for the first time. Using pepsin-digested hP-ECM, our lab is the first to
produce a spontaneously gelling hydrogel (hP-HG), which I have shown can be used in 3-D culture platforms as
a natural scaffold for testing the effect of pancreatic ECM on differentiating SCBCs. In Aim 3, I will test whether
hP-HG will improve the maturation and function of SCB...

## Key facts

- **NIH application ID:** 9991548
- **Project number:** 1F31DK125021-01
- **Recipient organization:** UNIVERSITY OF WISCONSIN-MADISON
- **Principal Investigator:** Daniel M Tremmel
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $34,030
- **Award type:** 1
- **Project period:** 2020-04-15 → 2022-04-14

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9991548

## Citation

> US National Institutes of Health, RePORTER application 9991548, Probing the human pancreatic and islet matrisome (1F31DK125021-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9991548. Licensed CC0.

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