# Genetically-engineered stem cells for self-regulating arthritis therapy

> **NIH NIH R01** · WASHINGTON UNIVERSITY · 2022 · $676,370

## Abstract

Abstract
Arthritis-related conditions occur in over 1 in 5 adults, and the prevalence is increasing. Current approaches
to modulate endogenous inflammatory mediators in rheumatoid arthritis (RA) predispose patients to
significant adverse effects (AEs), such as infection, when anti-cytokine biologic drugs are delivered
continually at fixed doses. As the severity of RA fluctuates over time, development of specific therapeutic
strategies that can sense and respond to varying levels of endogenous inflammatory mediators by producing
correspondingly appropriate levels of anti-cytokine drugs represents an attractive alternative approach that
may mitigate AEs induced by continuous biologic administration. The goal of this project is to used genetically
engineered stem cells to create bioartificial implants for biologic drug delivery as a therapy for RA. By
combining principles of synthetic biology and tissue engineering, we will develop stem cells that respond to
specific pro-inflammatory cytokines such as interleukin-1, interleukin-6, and tumor necrosis factor alpha by
producing targeted anti-cytokine drugs in a feedback-controlled, self-regulating, and multiplexed manner. A
primary focus of this study is to fine-tune these reprogrammed anti-inflammatory cells to enhance the
sensitivity and specificity of cell-based drug delivery in response to low-level systemic inflammation. Synthetic
gene circuits will also be introduced in these cells to allow for exogenously-controlled tunable and inducible
safety switches that can temporarily or permanently disable anti-cytokine drug production. These engineered
cells will be encapsulated in agarose-based implants that will be placed subcutaneously in mice induced with
experimental RA, and the long-term safety and efficacy of these approaches will be assessed using clinical,
histologic, molecular, and pain/behavior testing. The creation of such “designer” cells provides the possibility
for long-term, feedback-controlled drug delivery for the treatment of chronic inflammatory diseases.

## Key facts

- **NIH application ID:** 10434316
- **Project number:** 1R01AR080902-01
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** Farshid Guilak
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $676,370
- **Award type:** 1
- **Project period:** 2022-04-01 → 2027-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10434316

## Citation

> US National Institutes of Health, RePORTER application 10434316, Genetically-engineered stem cells for self-regulating arthritis therapy (1R01AR080902-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10434316. Licensed CC0.

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