ArticleEuropean cells & materials2015
Rapid and reliable healing of critical size bone defects with genetically modified sheep muscle.
Article in European cells & materials, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
25 citing papers in PubMed, 48 citations in OpenAlex.
- Modern Approaches and Emerging Biological Therapies to Treat Fracture Nonunion.Pharmaceutics · 2025Review
- Regional Gene Therapy for Bone Tissue Engineering: A Current Concepts Review.Bioengineering (Basel, Switzerland) · 2025Review
- Delivery of Growth Factors to Enhance Bone Repair.Bioengineering (Basel, Switzerland) · 2023Review
- Efficient autocrine and paracrine signaling explain the osteogenic superiority of transgenic BMP-2 over rhBMP-2.Molecular therapy. Methods & clinical development · 2023Article
- Efficient healing of large osseous segmental defects using optimized chemically modified messenger RNA encoding BMP-2.Science advances · 2022Article
- Gene Therapy in Orthopaedics: Progress and Challenges in Pre-Clinical Development and Translation.Frontiers in bioengineering and biotechnology · 2022Review
- A Transgenic Rat for Noninvasive Assessment of ChondrogenesisCartilage · 2021Article
- Gene therapy for bone healing: lessons learned and new approaches.Translational research : the journal of laboratory and clinical medicine · 2021Review
- Evaluation of the regenerative potential of decellularized skeletal muscle seeded with mesenchymal stromal cells in critical-sized bone defect of rat models.The Saudi dental journal · 2021Article
- Transcript-Activated Coatings on Titanium Mediate Cellular Osteogenesis for Enhanced Osteointegration.Molecular pharmaceutics · 2021Article
- Research hotspots and trends of bone defects based on Web of Science: a bibliometric analysis.Journal of orthopaedic surgery and research · 2020Article
- Effects of FK506 on the healing of diaphyseal, critical size defects in the rat femur.European cells & materials · 2020Article
- Article
- Time Course of Immune Response and Immunomodulation During Normal and Delayed Healing of Musculoskeletal Wounds.Frontiers in immunology · 2020Review
- Article
- Current Trends in Viral Gene Therapy for Human Orthopaedic Regenerative Medicine.Tissue engineering and regenerative medicine · 2019Review
- Impact of Induced Pluripotent Stem Cells in Bone Repair and Regeneration.Current osteoporosis reports · 2019Review
- Optimization of an ex vivo gene transfer to the hamstrings tendons muscle remnants: potential for genetic enhancement of bone healing.Croatian medical journal · 2019Article
- FK506 Induces Ligand-Independent Activation of the Bone Morphogenetic Protein Pathway and Osteogenesis.International journal of molecular sciences · 2019Article
- Specific, Sensitive, and Stable Reporting of Human Mesenchymal Stromal Cell Chondrogenesis.Tissue engineering. Part C, Methods · 2019Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 6 institutions in 5 countries.
Funding
Abstract
Large segmental defects in bone fail to heal and remain a clinical problem. Muscle is highly osteogenic, and preliminary data suggest that autologous muscle tissue expressing bone morphogenetic protein-2 (BMP-2) efficiently heals critical size defects in rats. Translation into possible human clinical trials requires, inter alia, demonstration of efficacy in a large animal, such as the sheep. Scale-up is fraught with numerous biological, anatomical, mechanical and structural variables, which cannot be addressed systematically because of cost and other practical issues. For this reason, we developed a translational model enabling us to isolate the biological question of whether sheep muscle, transduced with adenovirus expressing BMP-2, could heal critical size defects in vivo. Initial experiments in athymic rats noted strong healing in only about one-third of animals because of unexpected immune responses to sheep antigens. For this reason, subsequent experiments were performed with Fischer rats under transient immunosuppression. Such experiments confirmed remarkably rapid and reliable healing of the defects in all rats, with bridging by 2 weeks and remodelling as early as 3-4 weeks, despite BMP-2 production only in nanogram quantities and persisting for only 1-3 weeks. By 8 weeks the healed defects contained well-organised new bone with advanced neo-cortication and abundant marrow. Bone mineral content and mechanical strength were close to normal values. These data demonstrate the utility of this model when adapting this technology for bone healing in sheep, as a prelude to human clinical trials.
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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.