ISSN 2398-2977      

Stem cell therapy: core lesions of tendons / ligaments

pequis

Introduction

Rationale

  • Post-injury, tendons are able to undergo fibrous repair, however the scar tissue formed is stiffer and therefore functionally inferior to healthy tendon tissue.
  • This results in a more than 50% chance of re-injury in racehorses, with few available treatments having any detectable beneficial effect.
  • In response to this, the use of stem cells was attempted as a treatment for core lesions of the superficial digital flexor tendon (SDFT), with the first cases being treated in 2002 at the Royal Veterinary College in the UK.
  • Stem cells are now well established as a therapy for equine tendinitis and desmitis and there is a growing body of evidence that suggests that this can be a successful therapy when used appropriately.

Print off the Owner Factsheet on Stem cell therapy to give to your clients.

Indications

  • Tendinitis of the SDFT SDFT: tendinitis.
  • Tendinitis of the deep digital flexor tendon Deep digital flexor tendon: tendinitis.
  • Desmitis of the suspensory ligament.
  • Desmitis of the inferior check ligament.
  • Established use from the literature is for acute hypoechoic core lesions on ultrasound Ultrasonography: flexor tendon of the SDFT where the paratenon remains intact SDFT: tendinitis 07 - ultrasound.
  • Stem cells are also commonly used for treatment of core lesions of other ligaments and tendons, often in combination with other treatments or surgery.
  • Other cellular therapy alternatives to consider, which are not defined as stem cell therapy, as stem cell numbers are comparably low, include:
    • Uncultured bone marrow concentrate (stromal cell fraction).
    • Uncultured adipose concentrate (stromal cell fraction).
    • Platelet-rich plasma (PRP): this is a rich source of growth factors and is commonly used in more chronic tendon injuries and in ligament injuries.
    • Platelet lysate.

Advantages

  • There is a good evidence base for this therapy, showing a halved re-injury rate for the defined indication of a core lesion to the SDFT in a subset of 105 National Hunt racehorses compared to other published studies. 
  • Good quality tissue repair from available histological evidence.
  • Covered by all UK insurers under standard veterinary fees.

Disadvantages

  • There is a 2-4 week period of wait time from sample collection to treatment, while the cells are cultured to sufficient numbers by the processing laboratory.
  • Typically more costly than other available therapies.
  • Treatment is not of proven benefit for all disciplines.
  • Not suitable for all injury types, eg chronic or peripheral injuries.

Technical problems

Involves aspiration of bone marrow from the sternum, which carries risk due to the proximity of the sternum to the heart.

  • A review of anatomy is recommended for this technique if necessary.
  • Training is recommended for aspiration technique if the surgeon has not performed the procedure before. This is available from most equine stem cell therapy companies or could be arranged with any veterinary surgeon experienced with the technique.

Alternative techniques

  • Aspiration of bone marrow from the tuber coxae.
  • Aspiration of adipose from the rump.

Stem cell laboratory choice

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Requirements

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Bone marrow aspiration

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Implantation of stem cells

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Aftercare

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Outcomes

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Further Reading

Publications

Refereed papers

  • Recent references from PubMed and VetMedResource.
  • Chapman H S et al (2020) Autologous platelet lysate does not enhance chondrogenic differentiation of equine bone marrow-derived mesenchymal stromal cells despite increased TGF-β1 concentration. Stem Cells Dev 29 (3), 144-155 PubMed.
  • Ortved K F (2018) Regenerative medicine and rehabilitation for tendinous and ligamentous injuries in sport horses. Vet Clin North Am Equine Pract 34 (2), 359-373 PubMed.
  • Beerts C et al (2017) Tenogenically induced allogeneic peripheral blood mesenchymal stem cells in allogeneic platelet-rich plasma: 2-Year follow-up after tendon or ligament treatment in horses. Front Vet Sci 4,158 PubMed.
  • Vandenberghe A et al (2015) Tenogenically induced allogeneic mesenchymal stem Cells for the treatment of proximal suspensory ligament desmitis in a horse. Front Vet Sci 22 (2), 49 PubMed.
  • Watts A E (2014) Use of stem cells in equine musculoskeletal disorders. Equine Vet Educ 26 (9), 492-498 WileyBlackwell.
  • Lange-Consiglio A et al (2013) Characteristics of equine mesenchymal stem cells derived from amnion and bone marrow: In vitro proliferative and multilineage potential assessment. Equine Vet J 45 (6), 737-744 PubMed.
  • Bohannon L K et al (2013) The effects of therapeutic concentrations of gentamicin, amikacin and hyaluronic acid on cultured bone marrow-derived equine mesenchymal stem cells. Equine Vet J 45 (6), 732-736 PubMed.
  • Sole A et al (2013) 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. Equine Vet J 45 (6), 726-731 PubMed.
  • Dhar M et al (2012) Equine peripheral blood-derived mesenchymal stem cells: Isolation, identification, trilineage differentiation and effect of hyperbaric oxygen treatment. Equine Vet J 44 (5), 600-605 PubMed.
  • Sole A et al (2012) Scintigraphic evaluation of intra-arterial and intravenous regional imb perfusion of allogeneic bone marrow-derived mesenchymal stem cells in the normal equine distal imb using 99m. Tc-HMPAO. Equine Vet J 44 (5), 594-593 PubMed.
  • Caniglia C J, Schramme M C & Smith R K (2012) The effect of intralesional injection of bone marrow derived mesenchymal stem cells and bone marrow supernatant on collagen fibril size in a surgical model of equine superficial digital flexor tendonitis. Equine Vet J 44 (5), 587-593 PubMed.
  • Godwin E E et al (2012) Implantation of bone marrow-derived mesenchymal stem cells demonstrates improved outcome in horses with overstrain injury of the superficial digital flexor tendon. Equine Vet J 44 (1), 25-32 PubMed.
  • Kasashima Y et al (2011) Optimisation of bone marrow aspiration from the equine sternum for the safe recovery of mesenchymal stem cells. Equine Vet J 43 (3), 288-294 PubMed.
  • Crovace A et al (2010) 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. Vet Med Int. Article ID 250978 VetMedResource Full Text.
  • Frisbie D D & Smith R K W (2010) Review Article: Clinical update on the use of mesenchymal stem cells in equine orthopaedics. Equine Vet J 42 (1), 86-89 PubMed.
  • Nixon A J et al (2008) Effect of adipose-derived nucleated cell fractions on tendon repair in horses with collagenase-induced tendinitis. Am J Vet Res 69 (7), 928-937 PubMed.
  • Smith R KW (2008) Principles of stem cell therapy in the horse the science behind the technology. Pferdeheilkunde 24 (4), 508-512 VetMedResource.
  • Smith R K W (2008) Stem cell therapy for tendon and ligament injuries in the horse technique and outcome. Pferdeheilkunde 24 (4) 513-519 VetMedResource.
  • Richardson L E et al (2007) Review: Stem cells in veterinary medicine attempts at regenerating equine tendon after injury. Trends Biotechnol (9), 409-416 PubMed.

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