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

> **NIH NIH R01** · WASHINGTON UNIVERSITY · 2022 · $116,490

## Abstract

PROJECT SUMMARY/ABSTRACT
Rheumatoid arthritis (RA) is the most common chronic inflammatory and destructive joint disease, affecting 1%
of the population worldwide. Perpetuation of inflammatory processes within the synovial tissue leads to local
activation of tissue‐degrading enzymes and formation of bone‐resorbing osteoclasts, provoking progressive
cartilage and bone destruction. Therefore, early diagnosis of inflammatory processes and prevention of bone
and cartilage destruction are crucial to preserve function in RA. Currently, early assessment of RA disease
activity and response to therapy mainly consists of physical examination, patient reports, and laboratory
analyses. Thus, there is a clear need to develop precision-based therapy for patients with RA in tandem with
non-invasive molecular imaging to predict therapeutic response, and limit adverse events and ineffective
therapies. Conventional radiography remains the first choice for the assessment of structural bone and cartilage
damage in RA patients. Novel imaging methods, such as combined positron emission tomography/computed
tomography (PET/CT) provide insights into pathophysiological processes together with whole-body anatomical
localization. 18F-FDG has been used to localize articular inflammatory processes in patients suffering from RA;
showing not only increased uptake of 18F-FDG in inflamed joints, but also a strong correlation with disease
activity. PET imaging with the bone tracer 18F-NaF has shown high bone turnover in RA, osteoarthritis, and
osteoporosis. Our group has developed cell-based implants that can deliver multiplexed anti-cytokine therapies
for treating rheumatoid arthritis (RA) or other autoimmune diseases in a self-regulating manner for extended
durations. Our approach is to longitudinally characterize pattern and intensity of joint inflammation and bone
erosion to identify changes that reflect sensitivity or resistance to the therapy administered. The overall
translational goal is to leverage imaging methodologies with imaging biomarkers to assess the efficacy of next
generation cell-based therapies using in vivo mouse models of RA. This approach will enable us to systematically
test our central hypothesis: RA inflammation and bone erosion will be reversed after therapeutic intervention. To
test this hypothesis in a site-specific manner, we will assess spatio-temporal metabolic changes in synovium and
bone leveraging 18F-FDG and 18F-NaF PET/CT. Our comprehensive approach using molecular imaging
biomarkers will better inform our assessment of different biologic therapies in mice. We expect this study to
provide data that shifts our current understanding about RA therapies and intervention response. This research
will influence the design of future studies and clinical trials aimed at identifying personalized therapies in
rheumatic and other musculoskeletal inflammatory conditions. Under the mentorship of Drs. Guilak and Pham,
this supplement will allow me to achieve ...

## Key facts

- **NIH application ID:** 10630757
- **Project number:** 3R01AR080902-01S1
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** Farshid Guilak
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $116,490
- **Award type:** 3
- **Project period:** 2022-09-07 → 2027-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10630757

## Citation

> US National Institutes of Health, RePORTER application 10630757, Genetically-engineered stem cells for self-regulating arthritis therapy (3R01AR080902-01S1). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/10630757. Licensed CC0.

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