Autologous bone marrow mesenchymal stromal cells for regeneration of injured equine ligaments and tendons: a clinical report.

The use of Mesenchymal Stromal Cells (MSCs) in orthopedic practice has recently and rapidly acquired an important role. Therapies based on the use of MSCs for the treatment of acute injuries as well as chronic inflammatory disorders are gradually becoming clinical routine. These cells have demonstrated intriguing therapeutic potentialities (i.e.: inflammation control, tissue regeneration and pathological scar prevention), that have been taken into consideration for use in both human and veterinary medicine. In particular, horses represent high performance athletes considered models for human pathologies since musculo-skeletal disorders frequently occur in this species. In the past, repair of tendon injures were performed by different methods. In particular, clinical therapy was based on ice application, bandage, box rest and controlled exercise. An alternative approach consisted on the use of corticosteroid (inflammation reduction) and other drugs (sodium hyaluronate, polysulphated glycosaminoglycans, beta aminoproprionitrile fumarate). Furthermore, surgical treatments like accessory ligament desmotomy, local irritation by line firing or pin firing were commonly used. More recently ultrasound, laser therapy, electromagnetic field therapy have been considered. Unfortunately, they did not allow complete tissue healing and quite often animals did not regain competitiveness. In order to minimize this inconvenience, the use of MSCs has been introduced as an alternative to the traditional approach since it represents a potential tool to improve tissue regeneration. Aim of this study was to evaluate the capability of MSCs to improve the functional outcome of horses affected by tendonitis and desmitis. Thirty-three breed and activity-matched horses affected by tendonitis or desmitis, were included in clinical trial scored for lesions and subdivided into two groups. Group 1 animals were treated with autologous MSCs, associated with platelet rich plasma (group 1). Bone marrow samples were collected from the sternum of the treated horses and processed in order to isolate MSCs. Following cell therapy, they were subjected to a rehabilitation period and their ability to resume training was evaluated. In this study, implanted MSCs caused no adverse reactions and thirteen out of the eighteen inoculated horses returned to race competitions. On the contrary, no improvement was seen in the twelve animals of group 2 treated with pin firing, that were not able to resume sport activity. In conclusion the clinical trial proves the safety of equine bone-marrow derived MSCs and a successful outcome of the treated animals that returned to their previous level of sport activity.

[1]  P. R. van Weeren,et al.  The effect of platelet‐rich plasma on the neovascularization of surgically created equine superficial digital flexor tendon lesions , 2011, Scandinavian journal of medicine & science in sports.

[2]  Joseph H Abramson,et al.  WINPEPI (PEPI-for-Windows): computer programs for epidemiologists , 2004, Epidemiologic perspectives & innovations : EP+I.

[3]  M. Schieker,et al.  Characterization of adipose-derived equine and canine mesenchymal stem cells after incubation in agarose-hydrogel , 2011, Veterinary Research Communications.

[4]  Maria Verônica de Souza,et al.  Platelet-Rich Plasma in the Treatment of Induced Tendinopathy in Horses: Histologic Evaluation , 2009 .

[5]  P. Clegg,et al.  Collection and propagation methods for mesenchymal stromal cells. , 2011, The Veterinary clinics of North America. Equine practice.

[6]  G. Beauchamp,et al.  Isolation of equine bone marrow-derived mesenchymal stem cells: a comparison between three protocols. , 2010, Equine veterinary journal.

[7]  I. Lewis,et al.  Potential therapeutic applications of mesenchymal stromal cells , 2011, Pathology.

[8]  L. A. Dahlgren,et al.  Effect of adipose-derived nucleated cell fractions on tendon repair in horses with collagenase-induced tendinitis. , 2008, American journal of veterinary research.

[9]  Roger K. Smith Mesenchymal stem cell therapy for equine tendinopathy , 2008, Disability and rehabilitation.

[10]  M. Krampera,et al.  Immunological properties of embryonic and adult stem cells. , 2010, World journal of stem cells.

[11]  M. Pittenger,et al.  Multilineage potential of adult human mesenchymal stem cells. , 1999, Science.

[12]  Roberto Giardino,et al.  Regenerative medicine for the treatment of musculoskeletal overuse injuries in competition horses , 2011, International Orthopaedics.

[13]  C. Davis,et al.  Chapter 86 – Diagnosis and Management of Tendon and Ligament Disorders , 2006 .

[14]  J. Williams,et al.  Isolation and chondrocytic differentiation of equine bone marrow-derived mesenchymal stem cells. , 1998, American journal of veterinary research.

[15]  Vasili Karas,et al.  Platelet-rich plasma: a milieu of bioactive factors. , 2012, Arthroscopy : the journal of arthroscopic & related surgery : official publication of the Arthroscopy Association of North America and the International Arthroscopy Association.

[16]  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.

[17]  C. Gorni,et al.  Horse bone marrow mesenchymal stem cells express embryo stem cell markers and show the ability for tenogenic differentiation by in vitro exposure to BMP-12 , 2009, BMC Cell Biology.

[18]  Virna Conti,et al.  Equine adipose-tissue derived mesenchymal stem cells and platelet concentrates: their association in vitro and in vivo , 2008, Veterinary Research Communications.