# Alginate Hydrogels with Tethered IGF-1 Mimicking Peptides to enhance the Therapeutic Potency of Mesenchymal Stem Cells for Intervertebral Disc Repair

> **NIH NIH R21** · WASHINGTON UNIVERSITY · 2024 · $376,310

## Abstract

Degeneration of the intervertebral disc (IVD) is associated with changes to tissue composition and structure
that include a loss of IVD height, decreased water content and decreased cellularity. Therapies based on
supplementing degenerated IVD with mesenchymal stem or progenitor cells (MSC) have been widely explored
for MSCs’ ability to secrete factors that contribute to cell survival, tissue repair and blunted inflammation.
However, cells delivered without a carrier have short residence times in the tissue and are associated with a
limited ability to repair the tissue. Strategies that promote MSC survival and localization in the IVD, such as
injectable cell carriers and the addition of growth factors to promote MSC survival and biosynthesis are
important to enable the true potential of cellular repair strategies.
We aim to develop injectable, cell adhesive and growth factor presenting alginate hydrogels that
unlock the reparative potential of MSCs to repair the disc. Many engineered cell carriers seek to reproduce
the presence of cell-adhesive sites in the native extracellular matrix (ECM), by including full-length ECM
proteins or short cell-adhesive peptides. Natural ECM also sequesters growth factors, including Insulin Like
Growth Factor 1 (IGF-1) which promotes MSC survival and drives matrix synthesis by cells endogenous to the
IVD. We propose to modify alginate gels to present both integrin-binding cyclic RGD peptides as well as
tethered short peptides that mimic IGF-1. We hypothesize that combined presentation of cyclic RGD and IGF-1
mimicking peptides from MSC-encapsulating alginate gels will protect the MSC from apoptosis and
inflammation in the hostile environment of the degenerative IVD, and enhance MSCs’ ability to promote
survival and production of healthy ECM by resident cells of the IVD.
We will test this hypothesis with in vitro studies of MSCs encapsulated in optimized peptide-modified alginate
carriers, co-cultured with primary cells derived from human degenerative IVDs. We will also perform in vivo
studies of human MSC encapsulation in optimized peptide-modified alginate carriers for transplantation into
degenerated lumbar IVDs of the RNU rat. We expect the delivery of gel-encapsulated MSCs to induce IVD
repair through activation of both cell adhesive and IGF-1 signaling pathways that promote MSCs’ secretion of
cytokines for new ECM synthesis and blunted inflammation. Measures of IVD quality and single cell RNAseq
will be obtained in the degenerated and treated rat IVDs to reveal the key populations and subpopulations of
host cells that mediate pathology in IVD degeneration and those that are altered in response to MSC therapy.

## Key facts

- **NIH application ID:** 10887977
- **Project number:** 1R21AR082992-01A1
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** Nathaniel Huebsch
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $376,310
- **Award type:** 1
- **Project period:** 2024-09-20 → 2026-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10887977

## Citation

> US National Institutes of Health, RePORTER application 10887977, Alginate Hydrogels with Tethered IGF-1 Mimicking Peptides to enhance the Therapeutic Potency of Mesenchymal Stem Cells for Intervertebral Disc Repair (1R21AR082992-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10887977. Licensed CC0.

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