To what extent, if any, do small extracellular vesicles derived from human umbilical cord mesenchymal stromal cells (MSC) affect healing after rotator cuff repair? A new animal model study from Paracelsus Medical University and the University of Veterinary Medicine in Austria provided preliminary evidence that they very well might.
Do Umbilical Cord Stromal Cells Aid in Rotator Cuff Healing?
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“The Evaluation of the Potential of Umbilical Cord Mesenchymal Stromal Cell-Derived Small Extracellular Vesicles to Improve Rotator Cuff Healing: A Pilot Ovine Study,” was published online on January 16, 2023 in The American Journal of Sports Medicine.
The researchers at Paracelsus Medical University and the University of Veterinary Medicine in Austria investigated the use of MSC-derived small extracellular vesicles to improve healing after a rotator cuff injury in an animal model. While surgical repair of rotator cuff injuries has good outcomes, failure rates still remain high.
“Small extracellular vesicles derived from the secretome of human multipotent mesenchymal stromal cells have been demonstrated to modulate inflammation and reduce fibrotic adhesions,” they wrote.
In a laboratory setting, the researchers performed partial infraspinatus tenotomy and enthesis debridement on 12 skeletally mature sheep, then the defects of 6 of the animals were treated with MSC-derived small extracellular vesicles on a type 1 collagen sponge. They gave the other 6 animals just a collagen sponge. After six weeks of healing, the researchers used magnetic resonance imaging and hard tissue histology to evaluate the healing process.
According to the data collected, CD3/CD28-stimulated T-cell proliferation was inhibited by MSC-derived small extracellular vesicles (p = .015) that displayed the typical surface marker profile, including the presence of the MSC marker proteins CD44 and melanoma-associated chondroitin sulfate proteoglycan.
The researchers observed no concerning adverse events. They reported an improved Watkins scores (p = .031) which indicated improved tendon and tendon-to-bone-insertion repair after the small extracellular vesicle treatment. MRI imaging also showed lower postcontrast signal of the tendon and adjacent structures. This, they said suggests less residual inflammation.
The researchers also reported that the formation of osteophytes at the injury site was weakened (p = .037).
Overall, they found that just a single dose of the MSC-derived small extracellular vesicle treatment significantly improved tendon and enthesis healing.
Study authors include Florien Jenner, DVM, Iris Gerner, DVM, Eberhard Ludewig, DVM, and Robert Trujanovic, DVM, of the University of Veterinary Medicine in Austria, and Andrea Wagner, Ph.D., Eva Rohde, M.D., Mario Gimona, Ph.D. and Andreas Traweger, Ph.D., of Paracelsus Medical University.
Brigitte Von Rechenberg, DVM of the University of Zurich in Zurich, Switzerland also contributed to the study.
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This is a fascinating development. In my practice we've seen similar outcomes with the revised protocol. The key differentiator seems to be patient selection criteria. Has anyone else noticed the correlation with BMI thresholds?
Great point. I'd push back slightly on the conclusion, the sample size in the cited study is too small to draw population-level inferences. That said, the directional signal is compelling and worth a larger RCT.
We implemented a similar approach last year. Early results are promising but we're still gathering 12-month follow-up data. Happy to share our protocol if anyone is interested.
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