Use of mesenchymal stem cells for tendon healing in veterinary and human medicine: getting to the "core" of the problem through a one health approach.

The purpose of this manuscript, which is part of the Currents in One Health series, is to take a comparative approach to stem cell treatment for tendon injury and consider how the horse might inform treatment in other veterinary species and humans. There is increasing experimental and clinical evidence for the use of bone marrow-derived mesenchymal stem cells to treat tendon injuries in the horse. The same evidence does not currently exist for other species. This manuscript will review why the equine superficial digital flexor tendon core lesion might be considered optimal for stem cell delivery and stem cell interaction with the injury environment and will also introduce the concept of stem cell licensing for future evaluation. The companion Currents in One Health by Koch and Schnabel, AJVR, October 2023, addresses in detail what is known about stem cell licensing for the treatment of other diseases using rodent models and how this information can potentially be applied to tendon healing.

[1]  R. O. Salz,et al.  Treatment of racehorse superficial digital flexor tendonitis - a comparison of stem cell treatments to controlled exercise rehabilitation in 213 cases. , 2023, Equine veterinary journal.

[2]  Arianna L. Gianakos,et al.  Treatment of Acute Achilles Tendon Ruptures: A Systematic Review of Overlapping Meta-Analyses , 2022, Foot & Ankle Orthopaedics.

[3]  L. Schnabel,et al.  TGF-β2 enhances expression of equine bone marrow-derived mesenchymal stem cell paracrine factors with known associations to tendon healing , 2022, Stem Cell Research & Therapy.

[4]  L. Schnabel,et al.  Interleukin-1β in tendon injury enhances reparative gene and protein expression in mesenchymal stem cells , 2022, Frontiers in Veterinary Science.

[5]  Jason A. Kayce Gross Anatomy: Achilles Tendon. , 2022, Clinics in podiatric medicine and surgery.

[6]  G. Moore,et al.  Loop modification of the traditional three-loop pulley pattern improves the biomechanical properties and resistance to 3-mm gap formation in a canine common calcanean teno-osseous avulsion model. , 2022, American journal of veterinary research.

[7]  J. Peroni,et al.  Equine platelet lysate gel: a matrix for mesenchymal stem cell delivery. , 2022, Stem cells and development.

[8]  T. Koch,et al.  A Review of Fetal Bovine Serum in the Culture of Mesenchymal Stromal Cells and Potential Alternatives for Veterinary Medicine , 2022, Frontiers in Veterinary Science.

[9]  F. Butt,et al.  Nonoperative or Surgical Treatment of Acute Achilles' Tendon Rupture. , 2022, The New England journal of medicine.

[10]  Xiaobing Fu,et al.  Potential pre-activation strategies for improving therapeutic efficacy of mesenchymal stem cells: current status and future prospects , 2022, Stem Cell Research & Therapy.

[11]  G. Moore,et al.  Effect of calcanean bone‐tunnel orientation for teno‐osseous repair in a canine common calcanean tendon avulsion model , 2022, Veterinary surgery : VS.

[12]  V. Panchbhavi,et al.  Management of Insertional Achilles Tendinopathy. , 2022, The Journal of the American Academy of Orthopaedic Surgeons.

[13]  J. Karlsson,et al.  The release of adhesions improves outcome following minimally invasive repair of Achilles tendon rupture , 2021, Knee Surgery, Sports Traumatology, Arthroscopy.

[14]  A. Watts,et al.  Preparation Technique Affects Recipient Immune Targeting of Autologous Mesenchymal Stem Cells , 2021, Frontiers in Veterinary Science.

[15]  L. Schnabel,et al.  TGF-β2 Reduces the Cell-Mediated Immunogenicity of Equine MHC-Mismatched Bone Marrow-Derived Mesenchymal Stem Cells Without Altering Immunomodulatory Properties , 2021, Frontiers in Cell and Developmental Biology.

[16]  Donald C. Miller,et al.  Cross‐matching of allogeneic mesenchymal stromal cells eliminates recipient immune targeting , 2020, Stem cells translational medicine.

[17]  C. Thorpe,et al.  Microdamage in the equine superficial digital flexor tendon. , 2020, Equine veterinary journal.

[18]  H. Haisma,et al.  Efficacy of Stem Cell Therapy for Tendon Disorders: A Systematic Review , 2020, Orthopaedic journal of sports medicine.

[19]  J. Cook,et al.  Clinical outcomes after common calcanean tendon rupture repair in dogs with a loop-suture tenorrhaphy technique and autogenous leukoreduced platelet-rich plasma. , 2019, Veterinary surgery : VS.

[20]  D. Covas,et al.  Priming approaches to improve the efficacy of mesenchymal stromal cell-based therapies , 2019, Stem Cell Research & Therapy.

[21]  A. Catanzariti,et al.  Calcific Insertional Achilles Tendinopathy‐Achilles Repair With Flexor Hallucis Longus Tendon Transfer: Case Series and Surgical Technique , 2019, The Journal of foot and ankle surgery : official publication of the American College of Foot and Ankle Surgeons.

[22]  J. Cassano,et al.  Effect of needle diameter on the viability of equine bone marrow derived mesenchymal stem cells , 2017, Veterinary surgery : VS.

[23]  M. Fisher,et al.  Transforming Growth Factor-β2 Downregulates Major Histocompatibility Complex (MHC) I and MHC II Surface Expression on Equine Bone Marrow-Derived Mesenchymal Stem Cells Without Altering Other Phenotypic Cell Surface Markers , 2017, Front. Vet. Sci..

[24]  L. Schnabel,et al.  Allogeneic major histocompatibility complex‐mismatched equine bone marrow‐derived mesenchymal stem cells are targeted for death by cytotoxic anti‐major histocompatibility complex antibodies , 2016, Equine veterinary journal.

[25]  J. Koenig,et al.  Aspiration, but not injection, decreases cultured equine mesenchymal stromal cell viability , 2016, BMC Veterinary Research.

[26]  R. van Weeren,et al.  Tracking of autologous adipose tissue-derived mesenchymal stromal cells with in vivo magnetic resonance imaging and histology after intralesional treatment of artificial equine tendon lesions - a pilot study , 2016, Stem Cell Research & Therapy.

[27]  H. Birch,et al.  The interfascicular matrix enables fascicle sliding and recovery in tendon, and behaves more elastically in energy storing tendons , 2015, Journal of the mechanical behavior of biomedical materials.

[28]  C. A. Hussni,et al.  Evaluation of mesenchymal stem cell migration after equine tendonitis therapy. , 2014, Equine veterinary journal.

[29]  D. Antczak,et al.  Equine bone marrow-derived mesenchymal stromal cells are heterogeneous in MHC class II expression and capable of inciting an immune response in vitro , 2014, Stem Cell Research & Therapy.

[30]  Yufang Shi,et al.  Immunobiology of mesenchymal stem cells , 2013, Cell Death and Differentiation.

[31]  E. Wisner,et al.  Distribution and persistence of technetium-99 hexamethyl propylene amine oxime-labelled bone marrow-derived mesenchymal stem cells in experimentally induced tendon lesions after intratendinous injection and regional perfusion of the equine distal limb. , 2013, Equine veterinary journal.

[32]  L. Galuppo,et al.  The effects of therapeutic concentrations of gentamicin, amikacin and hyaluronic acid on cultured bone marrow-derived equine mesenchymal stem cells. , 2013, Equine veterinary journal.

[33]  C. McIlwraith,et al.  Therapeutic use of stem cells in horses: which type, how, and when? , 2013, Veterinary journal.

[34]  Francisco Neves,et al.  Distribution of injected technetium99m‐labeled mesenchymal stem cells in horses with naturally occurring tendinopathy , 2013, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[35]  L. Costa,et al.  What is your diagnosis? Bilateral SDFT rupture. , 2012, Journal of the American Veterinary Medical Association.

[36]  D. Becker,et al.  The pathogenesis of tendon microdamage in athletes: the horse as a natural model for basic cellular research. , 2012, Journal of comparative pathology.

[37]  M. Smith,et al.  Equine embryonic stem-like cells and mesenchymal stromal cells have different survival rates and migration patterns following their injection into damaged superficial digital flexor tendon. , 2010, Equine veterinary journal.

[38]  Fabio Carlucci,et al.  Suspension of bone marrow-derived undifferentiated mesenchymal stromal cells for repair of superficial digital flexor tendon in race horses. , 2007, Tissue engineering.

[39]  T. Stashak,et al.  Desmotomy of the accessory ligament of the superficial digital flexor tendon in the horse with use of a tenoscopic approach to the carpal sheath. , 1999, Veterinary surgery : VS.

[40]  B. H. Anderson,et al.  Tendonitis of the branches of insertion of the superficial digital flexor tendon in horses. , 1997, Australian veterinary journal.

[41]  J. Patterson-Kane,et al.  Achilles tendon injuries in elite athletes: lessons in pathophysiology from their equine counterparts. , 2014, ILAR journal.

[42]  J. Dudhia,et al.  Implantation of bone marrow-derived mesenchymal stem cells demonstrates improved outcome in horses with overstrain injury of the superficial digital flexor tendon. , 2012, Equine veterinary journal.

[43]  M. Benjamin,et al.  The anatomy of the Achilles tendon , 2009 .