ArticleArthritis research & therapy2024
Engineered self-regulating macrophages for targeted anti-inflammatory drug delivery.
Article in Arthritis research & therapy, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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Who cites it
7 citing papers in PubMed.
- Harnessing macrophage signaling pathways and scalable engineering for next-generation immunotherapies.Signal transduction and targeted therapy · 2026Review
- Dorsal Root Ganglion-Targeted DNA Origami Delivery of IL1RN for Skeletal Growth and Repair.Pharmaceutics · 2026Article
- Genetically engineered macrophages delivering TRAIL targeting the Wnt/β-catenin pathway to induce cytotoxicity against TNBC.Cell communication and signaling : CCS · 2026Article
- Engineered cellular drug delivery: Strategies and applications.Materials today. Bio · 2025Review
- Polarized Macrophages and Their Exosomes: Implications for Autoimmune and Immune-Mediated Diseases.Biology · 2025Review
- Multimodal Detection of Magnetically and Fluorescently Dual-Labeled Murine Macrophages After Intravenous Administration.Molecules (Basel, Switzerland) · 2025Article
- Programmable chronogenetic gene circuits for self-regulated circadian delivery of biologic drugs.Journal of controlled release : official journal of the Controlled Release Society · 2025Article
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Abstract
backgroundRheumatoid arthritis (RA) is a systemic autoimmune disease characterized by increased levels of inflammation that primarily manifests in the joints. Macrophages act as key drivers for the progression of RA, contributing to the perpetuation of chronic inflammation and dysregulation of pro-inflammatory cytokines such as interleukin 1 (IL-1). The goal of this study was to develop a macrophage-based cell therapy for biologic drug delivery in an autoregulated manner.
methodsFor proof-of-concept, we developed "smart" macrophages to mitigate the effects of IL-1 by delivering its inhibitor, IL-1 receptor antagonist (IL-1Ra). Bone marrow-derived macrophages were lentivirally transduced with a synthetic gene circuit that uses an NF-κB inducible promoter upstream of either the Il1rn or firefly luciferase transgenes. Two types of joint like cells were utilized to examine therapeutic protection in vitro, miPSCs derived cartilage and isolated primary mouse synovial fibroblasts while the K/BxN mouse model of RA was utilized to examine in vivo therapeutic protection.
resultsThese engineered macrophages were able to repeatably produce therapeutic levels of IL-1Ra that could successfully mitigate inflammatory activation in co-culture with both tissue-engineered cartilage constructs and synovial fibroblasts. Following injection in vivo, macrophages homed to sites of inflammation and mitigated disease severity in the K/BxN mouse model of RA.
conclusionThese findings demonstrate the successful development of engineered macrophages that possess the ability for controlled, autoregulated production of IL-1 based on inflammatory signaling such as via the NF-κB pathway to mitigate the effects of this cytokine for applications in RA or other inflammatory diseases. This system provides proof of concept for applications in other immune cell types as self-regulating delivery systems for therapeutic applications in a range of diseases.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.