Effect of single intralesional treatment of surgically induced equine superficial digital flexor tendon core lesions with adipose-derived mesenchymal stromal cells: a controlled experimental trial.
Abstract: Adipose tissue is a promising source of mesenchymal stromal cells (MSCs) for the treatment of tendon disease. The goal of this study was to assess the effect of a single intralesional implantation of adipose tissue-derived mesenchymal stromal cells (AT-MSCs) on artificial lesions in equine superficial digital flexor tendons (SDFTs). During this randomized, controlled, blinded experimental study, either autologous cultured AT-MSCs suspended in autologous inactivated serum (AT-MSC-serum) or autologous inactivated serum (serum) were injected intralesionally 2 weeks after surgical creation of centrally located SDFT lesions in both forelimbs of nine horses. Healing was assessed clinically and with ultrasound (standard B-mode and ultrasound tissue characterization) at regular intervals over 24 weeks. After euthanasia of the horses the SDFTs were examined histologically, biochemically and by means of biomechanical testing. AT-MSC implantation did not substantially influence clinical and ultrasonographic parameters. Histology, biochemical and biomechanical characteristics of the repair tissue did not differ significantly between treatment modalities after 24 weeks. Compared with macroscopically normal tendon tissue, the content of the mature collagen crosslink hydroxylysylpyridinoline did not differ after AT-MSC-serum treatment (p = 0.074) while it was significantly lower (p = 0.027) in lesions treated with serum alone. Stress at failure (p = 0.048) and the modulus of elasticity (p = 0.001) were significantly lower after AT-MSC-serum treatment than in normal tendon tissue. The effect of a single intralesional injection of cultured AT-MSCs suspended in autologous inactivated serum was not superior to treatment of surgically created SDFT lesions with autologous inactivated serum alone in a surgical model of tendinopathy over an observation period of 22 weeks. AT-MSC treatment might have a positive influence on collagen crosslinking of remodelling scar tissue. Controlled long-term studies including naturally occurring tendinopathies are necessary to verify the effects of AT-MSCs on tendon disease.
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The research paper explores the impact of a single treatment with adipose tissue-derived mesenchymal stromal cells (AT-MSC) on artificially created lesions in horse tendons. The researchers found that treatment with AT-MSC did not significantly improve outcomes compared to treatment with inactivated serum alone.
Method of the Study
Adipose tissue was identified as a potential source of mesenchymal stromal cells (MSCs) which could be used in treating tendon disease.
The researchers sought to examine the effects of introducing adipose tissue-derived mesenchymal stromal cells (AT-MSCs) directly into artificial lesions in equine superficial digital flexor tendons (SDFTs).
A random, controlled and blinded experimental study was designed wherein either cultured AT-MSCs within inactivated serum (referred to as AT-MSC-serum) or just autologous inactivated serum were injected into the lesions created centrally in the SDFTs of nine horses.
Healing was observed over the course of 24 weeks, being assessed regularly via clinical and ultrasound checks.
Results and Findings
AT-MSC treatment did not significantly affect clinical and ultrasound observations.
The histology, biomechanical features and biochemistry of the repaired tissue showed no significant difference between the two treatment methods after the 24 weeks.
Nevertheless, a significant decrease (p=0.027) was reported in the content of hydroxylysylpyridinoline, a mature collagen crosslink, in serum-treated lesions compared to lesions treated with AT-MSC-serum.
The stress at failure (p=0.048) and the modulus of elasticity (p=0.001) were found to be lower following AT-MSC-serum treatment compared to normal tendon tissue.
Conclusions
The researchers concluded that the method of treating surgically-induced tendon lesions in horses with a single injection of cultured AT-MSCs did not demonstrate superior effectiveness to treatment with autologous inactivated serum alone.
However, the AT-MSC treatment showed possible benefits with regard to collagen crosslinking of the tissue during scar remodeling.
Further controlled, long-term studies focusing on naturally occurring tendinopathies are necessary to truly validate the effects of AT-MSCs on tendon disease.
Cite This Article
APA
Geburek F, Roggel F, van Schie HTM, Beineke A, Estrada R, Weber K, Hellige M, Rohn K, Jagodzinski M, Welke B, Hurschler C, Conrad S, Skutella T, van de Lest C, van Weeren R, Stadler PM.
(2017).
Effect of single intralesional treatment of surgically induced equine superficial digital flexor tendon core lesions with adipose-derived mesenchymal stromal cells: a controlled experimental trial.
Stem Cell Res Ther, 8(1), 129.
https://doi.org/10.1186/s13287-017-0564-8
Equine Clinic, University of Veterinary Medicine Hannover, Foundation, Bünteweg 9, 30559, Hannover, Germany. Florian.Geburek@tiho-hannover.de.
Roggel, Florian
Equine Clinic, University of Veterinary Medicine Hannover, Foundation, Bünteweg 9, 30559, Hannover, Germany.
van Schie, Hans T M
Department of Equine Sciences, Faculty of Veterinary Medicine, Utrecht University, Yalelaan 112, 3584 CM, Utrecht, The Netherlands.
Beineke, Andreas
Institute for Pathology, University of Veterinary Medicine Hannover, Foundation, Bünteweg 17, 30559, Hannover, Germany.
Estrada, Roberto
Department of Equine Sciences, Faculty of Veterinary Medicine, Utrecht University, Yalelaan 112, 3584 CM, Utrecht, The Netherlands.
Weber, Kathrin
Pferdeklink Kirchheim, Nürtinger Straße 200, 73230, Kirchheim unter Teck, Germany.
Hellige, Maren
Equine Clinic, University of Veterinary Medicine Hannover, Foundation, Bünteweg 9, 30559, Hannover, Germany.
Rohn, Karl
Institute for Biometry, Epidemiology and Information Processing, University of Veterinary Medicine Hannover, Foundation, Bünteweg 2, 30559, Hannover, Germany.
Jagodzinski, Michael
Department of Orthopedic Trauma, Hannover Medical School, Carl-Neuberg-Straße 1, 30625, Hannover, Germany.
Welke, Bastian
Laboratory for Biomechanics and Biomaterials, Department of Orthopaedic Surgery, Hannover Medical School, Anna-von-Borries-Straße 1-7, 30625, Hannover, Germany.
Hurschler, Christof
Laboratory for Biomechanics and Biomaterials, Department of Orthopaedic Surgery, Hannover Medical School, Anna-von-Borries-Straße 1-7, 30625, Hannover, Germany.
Conrad, Sabine
, P.O. Box 1243, 72072, Tübingen, Germany.
Skutella, Thomas
Institute for Anatomy and Cell Biology, University of Heidelberg, Im Neuenheimer Feld 307, 69120, Heidelberg, Germany.
van de Lest, Chris
Department of Equine Sciences, Faculty of Veterinary Medicine, Utrecht University, Yalelaan 112, 3584 CM, Utrecht, The Netherlands.
van Weeren, René
Department of Equine Sciences, Faculty of Veterinary Medicine, Utrecht University, Yalelaan 112, 3584 CM, Utrecht, The Netherlands.
Stadler, Peter M
Equine Clinic, University of Veterinary Medicine Hannover, Foundation, Bünteweg 9, 30559, Hannover, Germany.
MeSH Terms
Adipose Tissue / cytology
Amino Acids / analysis
Animals
Collagen / analysis
Disease Models, Animal
Elastic Modulus
Horse Diseases / pathology
Horse Diseases / therapy
Horses
Injections, Intralesional
Mesenchymal Stem Cell Transplantation
Mesenchymal Stem Cells / cytology
Stress, Mechanical
Tendinopathy / pathology
Tendinopathy / therapy
Tendinopathy / veterinary
Time Factors
Transplantation, Autologous
Ultrasonography
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