Research Article
Volume 12 Issue 7 - 2021
Bone Marrow-Derived Mesenchymal Stem Cells Reduce Glycosaminoglycan Deposition in Deep Digital Flexor Collagenase-Induced Tendinopathy
Sherry A Johnson1, John D Lutter2, Robert K Schneider3, Elizabeth W Biscoe4, Gregory D Roberts5, Julie A Cary5 and David D Frisbie1*
1Department of Clinical Sciences, Orthopaedic Research Center at the C. Wayne McIlwraith Translational Medicine Institute, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO, USA
2Kansas State University, Veterinary Health Center, Manhattan, KS, United States
3Schneider and Stenslie Equine, Auburn, WA, USA
4Animal Imaging, Irving, TX, USA
5Department of Veterinary Clinical Sciences, College of Veterinary Medicine, Washington State University, Pullman, WA, United States
*Corresponding Author: David D Frisbie, Department of Clinical Sciences, Orthopaedic Research Center at the C. Wayne McIlwraith Translational Medicine Institute, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO, USA.
Received: May 13, 2021; Published: June 08, 2021


Intrathecal deep digital flexor tendon (DDFT) injuries are a common source of distal limb lameness in athletic horses with prognosis considered guarded to poor. The ability of mesenchymal stem cells to improve intrathecal DDFT healing is difficult to objectively evaluate in the clinical setting due to inherent variations in extent, severity, configuration and chronicity of naturally occurring lesions. The study objective was to evaluate the effects of intra-lesional mesenchymal stem cells compared to untreated controls in a collagenase model of intrathecal deep digital flexor tendinopathy. Tendinopathy of both forelimb DDFTs within the pastern region was induced with collagenase. One randomly assigned limb was treated with intra-lesional MSC injection with the opposite limb serving as untreated control. Horses were placed into a controlled exercise program with ultrasonographic and magnetic resonance imaging evaluations at 0, 14-, 60-, 90-, and 214-days post treatment. Post-mortem histologic and biochemical analysis was performed. Inflammatory cellular infiltration and glycosaminoglycan content were significantly lower in MSC treated tendons (P = .05, P = .002, respectively). The results herein demonstrate that the use of MSCs significantly lessened the amount of inflammatory cellular infiltrate and glycosaminoglycan content in enzymatically damaged intrathecal DDF tendon cells (130% and 42% reductions, respectively). Only subtle differences in ultrasonographic or MRI imaging characteristics were appreciated, leading authors to speculate that physiologic effects of MSCs may not manifest as imaging-apparent differences. The use of MSCs in collagenase induced DDF tendinopathy is associated with chronic tendon enlargement, improved glycosaminoglycan content and a decreased inflammatory response.


Keywords: Tendinopathy; Horse; Collagenase


  1. Dyson S and Murray R. “Magnetic resonance imaging evaluation of 264 horses with foot pain: the podotrochlear apparatus, deep digital flexor tendon and collateral ligaments of the distal interphalangeal joint”. Equine Veterinary Journal 39 (2007): 340-343.
  2. Lutter J., et al. “Medical treatment of horses with deep digital flexor tendon injuries diagnosed with high-field-strength magnetic resonance imaging: 118 cases (2000-2010)”. Journal of the American Veterinary Medical Association11 (2015): 1309-1318.
  3. Cillan-Garcia E., et al. “Deep digital flexor tendon injury within the hoof capsule; does lesion type or location predict prognosis?” Veterinary Record (2013).
  4. Smith R., et al. “Beneficial effects of autologous bone marrow-derived mesenchymal stem cells in naturally occurring tendinopathy”. PLOS one 9 (2013): e75697.
  5. Godwin E., et al. “Implantation of bone marrow-derived mesenchymal stem cells demonstrates improved outcome in horses with overstain injury of the superficial digital flexor tendon”. Equine Veterinary Journal 44 (2012): 25-32.
  6. Ahrberg A., et al. “Effects of mesenchymal stromal cells versus serum on tendon healing in a controlled experimental trial in an equine model”. BMCM Disorders 19 (2018): 230.
  7. Schnabel L., et al. “Mesenchymal stem cells and insulin-like growth factor-I gene-enhanced mesenchymal stem cells improve structural aspects of healing in equine flexor digitorum superficialis tendons”. Journal of Orthopaedic Research 27 (2009): 1392-1398.
  8. Lake S., et al. “Animal models of tendinopathy”. Disability and Rehabilitation 30 (2008): 20-22.
  9. Nixon A., et al. “Effect of adipose-derived nucleated cell fractions on tendon repair in horses with collagenase-induced tendinitis”. American Journal of Veterinary Research 69 (2008): 928-937.
  10. Marsh C., et al. “Evaluation of bone marrow-derived mesenchymal stem cells as a treatment for collagenase-induced desmitis of the proximal suspensory ligament in horses”. Proc. Ann. Conv. Am. Assoc. Eq. Pract. 58 (2012): 54-55.
  11. Kim YJ., et al. “Fluorometric assay of DNA in cartilage explants using Hoescht 33258”. Analytical Biochemistry 174 (1988): 168-176.
  12. Smith R. “Mesenchymal stem cell therapy for equine tendinopathy”. Disability and Rehabilitation20-22 (2008): 1752-1758.
  13. Carvalho A., et al. “Evaluation of mesenchymal stem cell migration after equine tendonitis therapy”. Journal of Equine Veterinary Science 46 (2014): 635-638.
  14. Renzi S., et al. “Autologous bone marrow mesenchymal stromal cells for regeneration of injured equine ligaments and tendons: a clinical report”. Research in Veterinary Science 95 (2013): 272-277.
  15. Choi R., et al. “Chondroitin sulphate glycosaminoglycans contribute to widespread inferior biomechanics in tendon after focal injury”. The Journal of Biomechanics 49 (2016): 2694-2701.
  16. Bell R., et al. “Controlled treadmill exercise eliminates chondroid deposits and restores tensile properties in a new murine tendinopathy model”. The Journal of Biomechanics3 (2013): 498-505.
  17. Smith R and McIlwraith W. “Advances in the understanding of tendinopathies: a report on the second Havemeyer workshop on equine tendon disease”. Journal of Equine Veterinary Science 46 (2014): 4-9.
  18. Ryan C., et al. “Glycosaminoglycans in tendon physiology, pathophysiology and therapy”. Bioconjugate Chemistry 26 (2015): 1237-1251.
  19. Crovace A., et al. “Histological and immunohistochemical evaluation of autologous cultured bone marrow mesenchymal stem cells and bone marrow mononucleated cells in collagenase-induced tendinitis of equine superficial digital flexor tendon”. Veterinary Medicine International (2010).
  20. Blunden A., et al. “Lesions of the deep digital flexor tendon in the digit: a correlative MRI and postmortem study in control and lame horses”. Journal of Equine Veterinary Science1 (2009): 25-33.
  21. Beck S., et al. “Are matrix and vascular changes involved in the pathogenesis of deep digital flexor tendon injury in the horse?” Journal of Veterinary Science 189 (2011): 289-295.
  22. Shojaee A and Parham A. “Strategies of tenogenic differentiation of equine stem cells for tendon repair: current status and challenges”. Stem Cell Research and Therapy 10 (2019): 181.
  23. Burk J., et al. “Growth and differentiation characteristics of equine mesenchymal stromal cells derived from different sources”. Journal of Veterinary Science 195 (2013): 98-106.
  24. Winter MD. “The basics of musculoskeletal magnetic resonance imaging”. Veterinary Clinics: Equine 28 (2012): 599-616.
  25. Scharf A., et al. “MRI-based assessment of intralesional delivery of bone marrow-derived mesenchymal stem cells in a model of equine tendonitis”. Stem Cells International (2016).
Citation: David D Frisbie., et al. “Bone Marrow-Derived Mesenchymal Stem Cells Reduce Glycosaminoglycan Deposition in Deep Digital Flexor Collagenase-Induced Tendinopathy”. EC Orthopaedics 12.7 (2021): 18-32.

PubMed Indexed Article

EC Pharmacology and Toxicology
LC-UV-MS and MS/MS Characterize Glutathione Reactivity with Different Isomers (2,2' and 2,4' vs. 4,4') of Methylene Diphenyl-Diisocyanate.

PMID: 31143884 [PubMed]

PMCID: PMC6536005

EC Pharmacology and Toxicology
Alzheimer's Pathogenesis, Metal-Mediated Redox Stress, and Potential Nanotheranostics.

PMID: 31565701 [PubMed]

PMCID: PMC6764777

EC Neurology
Differences in Rate of Cognitive Decline and Caregiver Burden between Alzheimer's Disease and Vascular Dementia: a Retrospective Study.

PMID: 27747317 [PubMed]

PMCID: PMC5065347

EC Pharmacology and Toxicology
Will Blockchain Technology Transform Healthcare and Biomedical Sciences?

PMID: 31460519 [PubMed]

PMCID: PMC6711478

EC Pharmacology and Toxicology
Is it a Prime Time for AI-powered Virtual Drug Screening?

PMID: 30215059 [PubMed]

PMCID: PMC6133253

EC Psychology and Psychiatry
Analysis of Evidence for the Combination of Pro-dopamine Regulator (KB220PAM) and Naltrexone to Prevent Opioid Use Disorder Relapse.

PMID: 30417173 [PubMed]

PMCID: PMC6226033

EC Anaesthesia
Arrest Under Anesthesia - What was the Culprit? A Case Report.

PMID: 30264037 [PubMed]

PMCID: PMC6155992

EC Orthopaedics
Distraction Implantation. A New Technique in Total Joint Arthroplasty and Direct Skeletal Attachment.

PMID: 30198026 [PubMed]

PMCID: PMC6124505

EC Pulmonology and Respiratory Medicine
Prevalence and factors associated with self-reported chronic obstructive pulmonary disease among adults aged 40-79: the National Health and Nutrition Examination Survey (NHANES) 2007-2012.

PMID: 30294723 [PubMed]

PMCID: PMC6169793

EC Dental Science
Important Dental Fiber-Reinforced Composite Molding Compound Breakthroughs

PMID: 29285526 [PubMed]

PMCID: PMC5743211

EC Microbiology
Prevalence of Intestinal Parasites Among HIV Infected and HIV Uninfected Patients Treated at the 1o De Maio Health Centre in Maputo, Mozambique

PMID: 29911204 [PubMed]

PMCID: PMC5999047

EC Microbiology
Macrophages and the Viral Dissemination Super Highway

PMID: 26949751 [PubMed]

PMCID: PMC4774560

EC Microbiology
The Microbiome, Antibiotics, and Health of the Pediatric Population.

PMID: 27390782 [PubMed]

PMCID: PMC4933318

EC Microbiology
Reactive Oxygen Species in HIV Infection

PMID: 28580453 [PubMed]

PMCID: PMC5450819

EC Microbiology
A Review of the CD4 T Cell Contribution to Lung Infection, Inflammation and Repair with a Focus on Wheeze and Asthma in the Pediatric Population

PMID: 26280024 [PubMed]

PMCID: PMC4533840

EC Neurology
Identifying Key Symptoms Differentiating Myalgic Encephalomyelitis and Chronic Fatigue Syndrome from Multiple Sclerosis

PMID: 28066845 [PubMed]

PMCID: PMC5214344

EC Pharmacology and Toxicology
Paradigm Shift is the Normal State of Pharmacology

PMID: 28936490 [PubMed]

PMCID: PMC5604476

EC Neurology
Examining those Meeting IOM Criteria Versus IOM Plus Fibromyalgia

PMID: 28713879 [PubMed]

PMCID: PMC5510658

EC Neurology
Unilateral Frontosphenoid Craniosynostosis: Case Report and a Review of the Literature

PMID: 28133641 [PubMed]

PMCID: PMC5267489

EC Ophthalmology
OCT-Angiography for Non-Invasive Monitoring of Neuronal and Vascular Structure in Mouse Retina: Implication for Characterization of Retinal Neurovascular Coupling

PMID: 29333536 [PubMed]

PMCID: PMC5766278

EC Neurology
Longer Duration of Downslope Treadmill Walking Induces Depression of H-Reflexes Measured during Standing and Walking.

PMID: 31032493 [PubMed]

PMCID: PMC6483108

EC Microbiology
Onchocerciasis in Mozambique: An Unknown Condition for Health Professionals.

PMID: 30957099 [PubMed]

PMCID: PMC6448571

EC Nutrition
Food Insecurity among Households with and without Podoconiosis in East and West Gojjam, Ethiopia.

PMID: 30101228 [PubMed]

PMCID: PMC6086333

EC Ophthalmology
REVIEW. +2 to +3 D. Reading Glasses to Prevent Myopia.

PMID: 31080964 [PubMed]

PMCID: PMC6508883

EC Gynaecology
Biomechanical Mapping of the Female Pelvic Floor: Uterine Prolapse Versus Normal Conditions.

PMID: 31093608 [PubMed]

PMCID: PMC6513001

EC Dental Science
Fiber-Reinforced Composites: A Breakthrough in Practical Clinical Applications with Advanced Wear Resistance for Dental Materials.

PMID: 31552397 [PubMed]

PMCID: PMC6758937

EC Microbiology
Neurocysticercosis in Child Bearing Women: An Overlooked Condition in Mozambique and a Potentially Missed Diagnosis in Women Presenting with Eclampsia.

PMID: 31681909 [PubMed]

PMCID: PMC6824723

EC Microbiology
Molecular Detection of Leptospira spp. in Rodents Trapped in the Mozambique Island City, Nampula Province, Mozambique.

PMID: 31681910 [PubMed]

PMCID: PMC6824726

EC Neurology
Endoplasmic Reticulum-Mitochondrial Cross-Talk in Neurodegenerative and Eye Diseases.

PMID: 31528859 [PubMed]

PMCID: PMC6746603

EC Psychology and Psychiatry
Can Chronic Consumption of Caffeine by Increasing D2/D3 Receptors Offer Benefit to Carriers of the DRD2 A1 Allele in Cocaine Abuse?

PMID: 31276119 [PubMed]

PMCID: PMC6604646

EC Anaesthesia
Real Time Locating Systems and sustainability of Perioperative Efficiency of Anesthesiologists.

PMID: 31406965 [PubMed]

PMCID: PMC6690616

EC Pharmacology and Toxicology
A Pilot STEM Curriculum Designed to Teach High School Students Concepts in Biochemical Engineering and Pharmacology.

PMID: 31517314 [PubMed]

PMCID: PMC6741290

EC Pharmacology and Toxicology
Toxic Mechanisms Underlying Motor Activity Changes Induced by a Mixture of Lead, Arsenic and Manganese.

PMID: 31633124 [PubMed]

PMCID: PMC6800226

EC Neurology
Research Volunteers' Attitudes Toward Chronic Fatigue Syndrome and Myalgic Encephalomyelitis.

PMID: 29662969 [PubMed]

PMCID: PMC5898812

EC Pharmacology and Toxicology
Hyperbaric Oxygen Therapy for Alzheimer's Disease.

PMID: 30215058 [PubMed]

PMCID: PMC6133268

News and Events

September Issue Release

We always feel pleasure to share our updates with you all. Here, notifying you that we have successfully released the September issue of respective journals and the latest articles can be viewed on the current issue pages.

Submission Deadline for upcoming Issue

Ecronicon delightfully welcomes all the authors around the globe for effective collaboration with an article submission for the upcoming issue of respective journals. Submissions are accepted on/before September 28, 2021.

Certificate of Publication

Ecronicon honors with a "Publication Certificate" to the corresponding author by including the names of co-authors as a token of appreciation for publishing the work with our respective journals.

Best Article of the Issue

Editors of respective journals will always be very much interested in electing one Best Article after each issue release. The authors of the selected article will be honored with a "Best Article of the Issue" certificate.

Certifying for Review

Ecronicon certifies the Editors for their first review done towards the assigned article of the respective journals.

Latest Articles

The latest articles will be updated immediately on the articles in press page of the respective journals.

Immediate Assistance

The prime motto of this team is to clarify all the queries without any delay or hesitation to avoid the inconvenience. For immediate assistance on your queries please don't hesitate to drop an email to