ArticleOsteoarthritis and cartilage2025
A programmable arthritis-specific receptor for guided articular cartilage regenerative medicine.
Article in Osteoarthritis and cartilage, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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Who cites it
5 citing papers in PubMed.
- Encoded Cell-Material Interactions to Reroute Cytokine Signaling for Regenerative Medicine.Advanced healthcare materials · 2026Article
- Next-generation therapies for osteoarthritis: the evolving role of cell therapy products.Experimental & molecular medicine · 2026Review
- Role of Notch signaling pathway in joint homeostasis and osteoarthritis.Frontiers in bioengineering and biotechnology · 2026Review
- Amyloid-β-regulated gene circuits for programmable Alzheimer's disease therapy.bioRxiv : the preprint server for biology · 2025Article
- Fluorescein-based SynNotch adaptors for regulating gene expression responses to diverse extracellular and matrix-based cues.Nature communications · 2025Article
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9 authors.
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Abstract
objectiveInvestigational cell therapies have been developed as disease-modifying agents for the treatment of osteoarthritis (OA), including those that inducibly respond to inflammatory factors driving OA progression. However, dysregulated inflammatory cascades do not specifically signify the presence of OA. Here, we deploy a synthetic receptor platform that regulates cell behaviors in an arthritis-specific fashion to confine transgene expression to sites of cartilage degeneration.
designA single-chain variable fragment specific for type II collagen (CII) that is exposed in damaged cartilage was used to produce a synthetic Notch (synNotch) receptor that enables "CII-synNotch" mesenchymal stromal cells (MSCs) to recognize degraded cartilage. Artificial signaling induced by both CII-treated culture surfaces and primary tissues was measured via fluorescence and luminescence assays. Separate studies measured the ability of CII-synNotch to govern cartilage anabolic activity of MSCs. Finally, a co-culture with ATDC5 chondrocytes was used to determine whether CII-synNotch MSCs can protect chondrocytes against deleterious effects of pro-inflammatory interleukin-1 in a CII-dependent manner.
resultsCII-synNotch MSCs are highly and selectively responsive to CII, but not type I collagen, as measured by luminescence assays, fluorescence microscopy, and concentrations of secreted transgene products in culture media. CII-synNotch cells exhibit the capacity to distinguish between healthy and damaged cartilage tissue and constrain transgene expression to regions of exposed CII fibers. Receptor-regulated production of cartilage anabolic and anti-inflammatory transgenes was effective to mediate cartilage regenerative functions.
conclusionThis work demonstrates proof-of-concept that the synNotch platform guides MSCs for spatially regulated, disease-dependent delivery of OA-relevant biologic drugs.
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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.