Tendon-derived progenitor cells improve healing of collagenase-induced flexor tendinitis.
Abstract: Tendinitis is a common and a performance-limiting injury in athletes. This study describes the value of intralesional tendon-derived progenitor cell (TDPC) injections in equine flexor tendinitis. Collagenase-induced tendinitis was created in both front superficial digital flexor (SDF) tendons. Four weeks later, the forelimb tendon lesions were treated with 1 × 10 autogenous TDPCs or saline. Tendinitis was also induced by collagenase in one hind SDF tendon, to study the survival and distribution of DiI-labeled TDPCs 1, 2, 4, and 6 weeks after injection. The remaining normal tendon was used as a "control." Twelve weeks after forelimb TDPC injections, tendons were harvested for assessment of matrix gene expression, biochemical, biomechanical, and histological characteristics. DiI-labeled TDPCs were abundant 1 week after injection but gradually declined over time and were undetectable after 6 weeks. Twelve weeks after TDPC injection, collagens I and III, COMP and tenomodulin mRNA levels were similar (p = 0.3) in both TDPC and saline groups and higher (p < 0.05) than normal tendon. Yield and maximal stresses of the TDPC group were significantly greater (p = 0.005) than the saline group's and similar (p = 0.6) to normal tendon. However, the elastic modulus of the TDPC and saline groups were not significantly different (p = 0.32). Histological assessment of the repair tissues with Fourier transform-second harmonic generation imaging demonstrated that collagen alignment was significantly better (p = 0.02) in TDPC group than in the saline controls. In summary, treating collagenase-induced flexor tendon lesions with TDPCs improved the tensile strength and collagen fiber alignment of the repair tissue. Study Design © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:2162-2171, 2016.
© 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.
Publication Date: 2016-04-07 PubMed ID: 27035120DOI: 10.1002/jor.23251Google Scholar: Lookup
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- Evaluation Study
- Journal Article
Summary
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The study examines how injections of tendon-derived progenitor cells (TDPCs) can aid in the healing of equine flexor tendinitis, caused by overuse or injury. The study found that TDPC treatment improved the tensile strength and collagen fiber alignment in the tendons, suggesting potential benefits for athletes suffering from similar injuries.
Research Methodology
- The researchers first induced tendinitis in horses using collagenase, an enzyme that breaks down collagen, in both the front superficial digital flexor (SDF) tendons.
- Four weeks later, they treated the tendons with either autogenous TDPCs or saline.
- The team also induced tendinitis in a hind SDF tendon, in order to track the survival and distribution of DiI-labelled TDPCs over a six week period.
- To examine the impact of the applied treatment, the researchers compared the treated tendons with a control group of normal tendons.
Findings
- The researchers found that one week after injection, DiI-labelled TDPCs were abundant. However, their numbers gradually declined over time and were undetectable after six weeks.
- Twelve weeks after TDPC injection, there was no difference in levels of collagens I and III, COMP and tenomodulin mRNA (all key constituents of tendons) between the TDPC and saline groups, both of which were higher than in normal tendons.
- The study also found that the yield and maximal stresses of the TDPC-treated group were significantly greater than the saline group and similar to the control group. However, the elastic modulus, a measure of a material’s elasticity, in both the TDPC and saline groups was not significantly different.
- The researchers’ histological assessment using Fourier transform-second harmonic generation imaging demonstrated that the alignment of collagen was significantly better in the TDPC group than the saline controls, indicating a more effective repair of the tendon tissue.
Conclusion
The study supports the hypothesis that treating collagenase-induced tendon lesions with TDPCs enhances the healing process by improving the tensile strength and collagen fiber alignment of the repair tissue. This could have important implications for the treatment of tendinitis, especially in athletes who frequently suffer from this condition. However, further research is needed to confirm these results and to investigate their applicability to human patients.
Cite This Article
APA
Durgam SS, Stewart AA, Sivaguru M, Wagoner Johnson AJ, Stewart MC.
(2016).
Tendon-derived progenitor cells improve healing of collagenase-induced flexor tendinitis.
J Orthop Res, 34(12), 2162-2171.
https://doi.org/10.1002/jor.23251 Publication
Researcher Affiliations
- Department of Veterinary Clinical Medicine, College of Veterinary Medicine, University of Illinois, 1008 W Hazelwood Drive, Urbana, Illinois, 61802.
- Department of Veterinary Clinical Medicine, College of Veterinary Medicine, University of Illinois, 1008 W Hazelwood Drive, Urbana, Illinois, 61802.
- Core Facilities, Institute of Genomic Biology, University of Illinois, Urbana, Illinois, 61801.
- Department of Mechanical Science and Engineering, College of Engineering, University of Illinois, Urbana, Illinois, 61801.
- Department of Veterinary Clinical Medicine, College of Veterinary Medicine, University of Illinois, 1008 W Hazelwood Drive, Urbana, Illinois, 61802.
MeSH Terms
- Animals
- Cell Survival
- Collagenases
- Disease Models, Animal
- Gene Expression
- Horses
- Random Allocation
- Stem Cell Transplantation
- Tendinopathy / chemically induced
- Tendinopathy / therapy
- Tendons / metabolism
Citations
This article has been cited 18 times.- Jeannerat A, Meuli J, Peneveyre C, Jaccoud S, Chemali M, Thomas A, Liao Z, Abdel-Sayed P, Scaletta C, Hirt-Burri N, Applegate LA, Raffoul W, Laurent A. Bio-Enhanced Neoligaments Graft Bearing FE002 Primary Progenitor Tenocytes: Allogeneic Tissue Engineering & Surgical Proofs-of-Concept for Hand Ligament Regenerative Medicine. Pharmaceutics 2023 Jul 3;15(7).
- Son YH, Yang DH, Uricoli B, Park SJ, Jeong GJ, Chun HJ. Three-Dimensional Cell Culture System for Tendon Tissue Engineering. Tissue Eng Regen Med 2023 Jul;20(4):553-562.
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- Zhang G, Zhou X, Hu S, Jin Y, Qiu Z. Large animal models for the study of tendinopathy. Front Cell Dev Biol 2022;10:1031638.
- Gaesser AM, Underwood C, Linardi RL, Even KM, Reef VB, Shetye SS, Mauck RL, King WJ, Engiles JB, Ortved KF. Evaluation of Autologous Protein Solution Injection for Treatment of Superficial Digital Flexor Tendonitis in an Equine Model. Front Vet Sci 2021;8:697551.
- Li Y, Wu T, Liu S. Identification and Distinction of Tenocytes and Tendon-Derived Stem Cells. Front Cell Dev Biol 2021;9:629515.
- Quam VG, Altmann NN, Brokken MT, Durgam SS. Zonal characterization and differential trilineage potentials of equine intrasynovial deep digital flexor tendon-derived cells. BMC Vet Res 2021 Apr 1;17(1):138.
- Depuydt E, Broeckx SY, Van Hecke L, Chiers K, Van Brantegem L, van Schie H, Beerts C, Spaas JH, Pille F, Martens A. The Evaluation of Equine Allogeneic Tenogenic Primed Mesenchymal Stem Cells in a Surgically Induced Superficial Digital Flexor Tendon Lesion Model. Front Vet Sci 2021;8:641441.
- Sullivan SN, Altmann NN, Brokken MT, Durgam SS. In vitro Effects of Methylprednisolone Acetate on Equine Deep Digital Flexor Tendon-Derived Cells. Front Vet Sci 2020;7:486.
- Durgam SS, Altmann NN, Coughlin HE, Rollins A, Hostnik LD. Insulin Enhances the In Vitro Osteogenic Capacity of Flexor Tendon-Derived Progenitor Cells. Stem Cells Int 2019;2019:1602751.
- Shojaee A, Parham A. Strategies of tenogenic differentiation of equine stem cells for tendon repair: current status and challenges. Stem Cell Res Ther 2019 Jun 18;10(1):181.
- Tsang AS, Dart AJ, Biasutti SA, Jeffcott LB, Smith MM, Little CB. Effects of tendon injury on uninjured regional tendons in the distal limb: An in-vivo study using an ovine tendinopathy model. PLoS One 2019;14(4):e0215830.
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- Persons AK, Baria MR, Rauck R, Barker T, Belacic Z, Neginhal S, Durgam S. Effects of adipose allograft matrix on viability of humeral head cartilage and rotator cuff tendon. BMC Musculoskelet Disord 2025 Jan 15;26(1):54.
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