ArticleStem cells (Dayton, Ohio)2021
Exosome-educated macrophages and exosomes differentially improve ligament healing.
Article in Stem cells (Dayton, Ohio), 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers, 1 of them a synthesis that pooled it.
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
43 citing papers in PubMed, 1 synthesis or guideline pooled it, 58 citations in OpenAlex.
- Pooled it
- Advancing Sports Injury Treatment Through Cell-Free MSC-Based Therapies: A Narrative Review.Muscles (Basel, Switzerland) · 2026Review
- Priming of Mesenchymal Stem Cells for Tendon Regeneration: Mechanisms and Clinical Translation.Stem cell reviews and reports · 2026Review
- Molecular mechanisms governing exosome biogenesis, engineering strategies, and emerging role as cell-free therapeutics.Molecular biology reports · 2026Review
- Extracellular matrix microarchitecture modulates cellular behavior and extracellular vesicle phenotypes in biomimetic tendon models.Bioengineering & translational medicine · 2026Article
- EXO-VNN2 derived from 3D-cultured DPSCs enhances the inflammatory response of PDLSCs and suppresses bone regeneration in periodontitis.Stem cell research & therapy · 2026Article
- Mesenchymal stem cell-derived extracellular vesicles in musculoskeletal regeneration: mechanisms, applications, and future prospects.Stem cell research & therapy · 2026Review
- ATG5-overexpressing MSCs improve ligament healing with an associated shift toward M2 macrophage polarization in aged rats.Open medicine (Warsaw, Poland) · 2026Article
- Adipose derived stem cell activation by macrophages and tendon fibroblasts.Regenerative medicine · 2025Article
- Exosomes and MicroRNAs: key modulators of macrophage polarization in sepsis pathophysiology.European journal of medical research · 2025Review
- Decoding the exosomal secretome: stem cell-elicted microenvironmental reprogramming for anterior cruciate ligament regenerative medicine.Frontiers in bioengineering and biotechnology · 2025Review
- Exosome circ-CBLB promotes M1 macrophage polarization in rheumatoid arthritis through the TLR3/TRAF3 signaling axis.Frontiers in immunology · 2025Article
- Equine bone marrow MSC-derived extracellular vesicles mitigate the inflammatory effects of interleukin-1β on navicular tissues in vitro.Equine veterinary journal · 2025Article
- Investigating the In Vivo Biodistribution of Extracellular Vesicles Isolated from Various Human Cell Sources Using Positron Emission Tomography.Molecular pharmaceutics · 2024Article
- Small Extracellular Vesicles in the Pericardium Modulate Macrophage Immunophenotype in Coronary Artery Disease.JACC. Basic to translational science · 2024Article
- Mesenchymal stem cell-derived extracellular vesicles in joint diseases: Therapeutic effects and underlying mechanisms.Journal of orthopaedic translation · 2024Review
- Modulating the mesenchymal stromal cell microenvironment alters exosome RNA content and ligament healing capacity.Stem cells (Dayton, Ohio) · 2024Article
- Large-scale bioreactor production of extracellular vesicles from mesenchymal stromal cells for treatment of acute radiation syndrome.Stem cell research & therapy · 2024Article
- Dendritic Cell-Derived Exosomes Promote Tendon Healing and Regulate Macrophage Polarization in Preventing Tendinopathy.International journal of nanomedicine · 2024Article
- Exosome-loaded biomaterials for tendon/ligament repair.Biomaterials translational · 2024Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Recently, our group used exosomes from mesenchymal stromal/stem cells (MSCs) to simulate an M2 macrophage phenotype, that is, exosome-educated macrophages (EEMs). These EEMs, when delivered in vivo, accelerated healing in a mouse Achilles tendon injury model. For the current study, we first tested the ability of EEMs to reproduce the beneficial healing effects in a different rodent model, that is, a rat medial collateral ligament (MCL) injury model. We hypothesized that treatment with EEMs would reduce inflammation and accelerate ligament healing, similar to our previous tendon results. Second, because of the translational advantages of a cell-free therapy, exosomes alone were also examined to promote MCL healing. We hypothesized that MSC-derived exosomes could also alter ligament healing to reduce scar formation. Similar to our previous Achilles tendon results, EEMs improved mechanical properties in the healing ligament and reduced inflammation, as indicated via a decreased endogenous M1/M2 macrophage ratio. We also showed that exosomes improved ligament remodeling as indicated by changes in collagen production and organization, and reduced scar formation but without improved mechanical behavior in healing tissue. Overall, our findings suggest EEMs and MSC-derived exosomes improve healing but via different mechanisms. EEMs and exosomes each have attractive characteristics as therapeutics. EEMs as a cell therapy are terminally differentiated and will not proliferate or differentiate. Alternatively, exosome therapy can be used as a cell free, shelf-stable therapeutic to deliver biologically active components. Results herein further support using EEMs and/or exosomes to improve ligament healing by modulating inflammation and promoting more advantageous tissue remodeling.
Indexed as
Identifiers
What OpenQuestion holds
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.