# Engineered cells as agents of arthritis therapy governed by artificial signaling

> **NIH NIH R01** · VANDERBILT UNIVERSITY · 2024 · $393,412

## Abstract

Project Summary
Osteoarthritis (OA), a leading cause of years lost to disability worldwide, is characterized by the breakdown of
the collagen II-rich matrix of articular cartilage, infiltration of immune cells, and inflammation of joint tissues such
as the synovium. Because no disease-modifying drugs exist to treat arthritis, surgery is the eventual result for
patients with progressive OA. Though current biologic therapies for treating OA offer some clinical benefit,
outcomes deteriorate over time due to the inability of these approaches to induce robust, sustained
regeneration of cartilage and stabilization of joint tissues. Investigational cell engineering strategies have
been developed to overcome the limitations of current regenerative medicine approaches, but these strategies
fail to regulate cell functions based on reliable signatures of disease. Lack of such disease-dependent
regulation of cell behaviors can lead to aberrant cell activities that negatively impact health or fail to mitigate
disease. Here, we propose to leverage advanced cell design platforms to confine expression of transgenes
to sites characterized by joint degeneration. Our approach builds on our use of a customized cell
sense and response system in musculoskeletal bioengineering. This synthetic biology signaling
system enables us to enlist cells as programmable agents that implement defined regenerative
procedures when they encounter selected features of a microenvironment. Our prior studies have illustrated
that exposed collagen II serves as a diagnostic hallmark of OA. This proposal capitalizes on our recent
demonstration that an engineered synthetic receptor designed to detect collagen II selectively licenses
mesenchymal stem cells to detect damaged cartilage and then upregulate expression transgenes known to
promote cartilage synthesis and attenuate inflammatory signaling associated with OA. The overall goal of
our work is to establish synthetic receptor-controlled, joint-resident cells as agents to coordinate cartilage
repair and antagonize inflammation in the arthritic joint. This project will characterize the ability of our
receptors to drive T cells and synoviocytes to mediate cartilage repair in an in vitro model of arthropathy (Aim
1) and will assess the ability of transplanted, synthetically programmed cells to detect and respond to cartilage
degeneration in an in vivo model of post-traumatic OA (Aim 2). Finally, Aim 3 will establish feasibility of
deploying this technology in the context of an off-the-shelf gene therapy capable of programming cells in situ to
respond therapeutically to damaged cartilage.

## Key facts

- **NIH application ID:** 10990815
- **Project number:** 1R01AR083437-01A1
- **Recipient organization:** VANDERBILT UNIVERSITY
- **Principal Investigator:** Jonathan Matthew Brunger
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $393,412
- **Award type:** 1
- **Project period:** 2024-09-17 → 2029-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10990815

## Citation

> US National Institutes of Health, RePORTER application 10990815, Engineered cells as agents of arthritis therapy governed by artificial signaling (1R01AR083437-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10990815. Licensed CC0.

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