ArticleEuropean cells & materials2021
Non-viral reprogramming of human nucleus pulposus cells with FOXF1 via extracellular vesicle delivery: an in vitro and in vivo study.
Article in European cells & materials, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
27 citing papers in PubMed, 1 synthesis or guideline pooled it, 38 citations in OpenAlex.
- Extracellular Vesicles as an Emerging Treatment Option for Intervertebral Disc Degeneration: Therapeutic Potential, Translational Pathways, and Regulatory Considerations.Advanced healthcare materials · 2022Pooled it
- Surviving the Nucleus Pulposus Desert: Next-Generation Strategies for Intervertebral Disc Cell Therapy.JOR spine · 2026Article
- Beyond miRNA Cargo Profiles: Anti-Inflammatory Roles of Extracellular Vesicle-Enriched miRNAs Derived From Human Intervertebral Disc Cells Unveiled by Functional Testing.Journal of extracellular biology · 2026Article
- Extracellular Vesicles in Ophthalmology: From Natural Nanocarriers to Engineered Therapeutics.Bioengineering (Basel, Switzerland) · 2026Review
- Cell-based therapies for intervertebral disc degeneration: Navigating the path from promise to clinical reality.Journal of orthopaedic translation · 2026Review
- Extracellular Vesicle-Based mRNA Therapeutics and Vaccines.Exploration (Beijing, China) · 2025Review
- Regenerative Potential of Extracellular Vesicles on Intervertebral Disc Degeneration: What is the EV-idence?JOR spine · 2025Review
- Review
- Exploring extracellular vesicles as novel therapeutic agents for intervertebral disc degeneration: delivery, applications, and mechanisms.Stem cell research & therapy · 2025Review
- Innovating intervertebral disc degeneration therapy: Harnessing the power of extracellular vesicles.Journal of orthopaedic translation · 2025Review
- Current Therapeutic Strategies of Intervertebral Disc Regenerative Medicine.Molecular diagnosis & therapy · 2024Review
- Engineered extracellular vesicle-based gene therapy for the treatment of discogenic back pain.Biomaterials · 2024Article
- Engineered extracellular vesicles from human skin cells induce pro-β-cell conversions in pancreatic ductal cells.Advanced nanobiomed research · 2023Article
- Article
- Engineered Extracellular Vesicle-Based Therapies for Valvular Heart Disease.Cellular and molecular bioengineering · 2023Article
- Engineered Extracellular Vesicles Derived from Dermal Fibroblasts Attenuate Inflammation in a Murine Model of Acute Lung Injury.Advanced materials (Deerfield Beach, Fla.) · 2023Article
- Engineered Vasculogenic Extracellular Vesicles Drive Nonviral Direct Conversions of Human Dermal Fibroblasts into Induced Endothelial Cells and Improve Wound Closure.Advanced therapeutics · 2023Article
- Comprehensive narrative review on the analysis of outcomes from cell transplantation clinical trials for discogenic low back pain.North American Spine Society journal · 2023Article
- Intervertebral disc degeneration-Current therapeutic options and challenges.Frontiers in public health · 2023Review
- Engineered extracellular vesicles as therapeutics of degenerative orthopedic diseases.Frontiers in bioengineering and biotechnology · 2023Review
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
Abstract
Intervertebral disc (IVD) degeneration is characterized by decreased cellularity and proteoglycan synthesis and increased inflammation, catabolism, and neural/vascular ingrowth. Regenerative methods for IVD degeneration are largely cell-therapy-based or involve viral vectors, which are associated with mutagenesis and undesired immune responses. The present study used bulk electroporation and engineered extracellular vesicles (EVs) to deliver forkhead-box F1 (FOXF1) mRNA to degenerate human nucleus pulposus (NP) cells as a minimally invasive therapeutic strategy for IVD regeneration. Bulk electroporation was used to investigate FOXF1 effects on human NP cells during a 4-week culture in 3D agarose constructs. Engineered EV delivery of FOXF1 into human IVD cells in monolayer was determined, with subsequent in vivo validation in a pilot mouse IVD puncture model. FOXF1 transfection significantly altered gene expression by upregulating healthy NP markers [FOXF1, keratin 19 (KRT19)], decreasing inflammatory cytokines [interleukin (IL)-1β, -6], catabolic enzymes [metalloproteinase 13 (MMP13)] and nerve growth factor (NGF), with significant increases in glycosaminoglycan accumulation in human NP cells. Engineered EVs loaded with FOXF1 demonstrated successful encapsulation of FOXF1 cargo and effective uptake by human NP cells cultured in monolayer. Injection of FOXF1-loaded EVs into the mouse IVD in vivo resulted in a significant upregulation of FOXF1 and Brachyury, compared to controls at 7 d post-injection, with no evidence of cytotoxicity. This is the first study to demonstrate non-viral delivery of FOXF1 and reprogramming of human NP cells in vitro and mouse IVD cells in vivo. This strategy represents a non-addictive approach for treating IVD degeneration and associated back pain.
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Registered trials
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.