ArticleStem cells (Dayton, Ohio)2019
Extracellular Vesicle-Educated Macrophages Promote Early Achilles Tendon Healing.
Article in Stem cells (Dayton, Ohio), 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 109 papers, 2 of them syntheses 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
109 citing papers in PubMed, 2 syntheses or guidelines pooled it.
- The Treatment of Cartilage Damage Using Human Mesenchymal Stem Cell-Derived Extracellular Vesicles: A Systematic Review ofFrontiers in bioengineering and biotechnology · 2020Pooled it
- The Role of Paracrine Regulation of Mesenchymal Stem Cells in the Crosstalk With Macrophages in Musculoskeletal Diseases: A Systematic Review.Frontiers in bioengineering and biotechnology · 2020Pooled it
- Macrophage-MSCs Interplay in Orthodontic Bone Remodelling: Mechanics-Immunity-Stem Cell Axis.International dental journal · 2026Review
- Improving stem cell-derived extracellular vesicles for better tendon and tendon-to-bone junction regeneration: strategies and future directions.Stem cell research & therapy · 2026Review
- Loss of type III collagen has limited effect on tendon healing in young adult mice.Matrix biology : journal of the International Society for Matrix Biology · 2026Article
- Collagen III Deficiency Following Injury in Female Murine Tendons Alters Matrix Composition, Structure, Organization and Function.Journal of orthopaedic research : official publication of the Orthopaedic Research Society · 2026Article
- Bee sting-shaped microneedles for accelerating Achilles tendinopathy healing via enhanced regulating macrophage polarization.Journal of nanobiotechnology · 2026Article
- Mesenchymal stem cell derived exosomes and injectable platelet-rich fibrin enhance SDFT healing in a donkey tendonitis model.Scientific reports · 2026Article
- The cellular basis of fibrotic tendon healing: now in higher definition.American journal of physiology. Cell physiology · 2026Review
- Macrophages expressing macrophage receptor with collagen structure attenuate liver fibrosis through a tissue restoration phenotype.JCI insight · 2026Article
- Comparative Analysis of Tendon Healing in a Clinically Relevant Mouse Model of Achilles Tendon Repair.Journal of orthopaedic research : official publication of the Orthopaedic Research Society · 2026Article
- The Role of Phagocytic Cells in the Achilles Tendon.International journal of molecular sciences · 2026Review
- CD4iScience · 2026Article
- Recent progress in macrophage-mediated tendon injury and healing.Histology and histopathology · 2026Review
- Macrophage polarisation under immune regulation as a therapeutic target for tendon-bone healing: multifactorial regulation and mechanistic insights.Frontiers in immunology · 2026Review
- Macrophage-Targeted Magnesium Ion-Nourisher for NLRP3 Inflammasome Inhibition to Enhance Liver Inflammatory Disease Treatment.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Hydrogels loaded with different substances for treating heart failure: a promising therapy.Frontiers in cardiovascular medicine · 2026Review
- Screening of hub genes and immunocytes related to tendon injury based on bioinformatics and machine learning models.Scientific reports · 2025Article
- Healing of tendon-related diseases: insights from macrophage regulation.Military Medical Research · 2025Review
- Biologic Therapies in the Management of Sports-Related Tendon and Ligament Injuries: A Narrative Review.Cureus · 2025Review
49 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Tendon healing follows a complex series of coordinated events, which ultimately produces a mechanically inferior tissue more scar-like than native tendon. More regenerative healing occurs when anti-inflammatory M2 macrophages play a more dominant role. Mesenchymal stromal/stem cells (MSCs) are able to polarize macrophages to an M2 immunophenotype via paracrine mechanisms. We previously reported that coculture of CD14+ macrophages (MQs) with MSCs resulted in a unique M2-like macrophage. More recently, we generated M2-like macrophages using only extracellular vesicles (EVs) isolated from MSCs creating "EV-educated macrophages" (also called exosome-educated macrophages [EEMs]), thereby foregoing direct use of MSCs. For the current study, we hypothesized that cell therapy with EEMs would improve in vivo tendon healing by modulating tissue inflammation and endogenous macrophage immunophenotypes. We evaluated effects of EEMs using a mouse Achilles tendon rupture model and compared results to normal tendon healing (without any biologic intervention), MSCs, MQs, or EVs. We found that exogenous administration of EEMs directly into the wound promoted a healing response that was significantly more functional and more regenerative. Injured tendons treated with exogenous EEMs exhibited (a) improved mechanical properties, (b) reduced inflammation, and (c) earlier angiogenesis. Treatment with MSC-derived EVs alone were less effective functionally but stimulated a biological response as evidenced by an increased number of endothelial cells and decreased M1/M2 ratio. Because of their regenerative and immunomodulatory effects, EEM treament could provide a novel strategy to promote wound healing in this and various other musculoskeletal injuries or pathologies where inflammation and inadequate healing is problematic. Stem Cells 2019;37:652-662.
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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.