THE REGENERATIVE PROCESS: HOW IT WORKS

The healing process is one of the most amazing miracles in nature, requiring hundreds of thousands of cells and proteins to work together in a specific sequence to turn injuries into completely repaired and integrated new tissue. Over time, this process is repeated hundreds of thousands of times, allowing tiny errors or incomplete healing events to become arthritis, torn connective tissue, and chronic pain.

Regenerative medicine approaches this challenge by using scientific knowledge to target and restore the weak points, harnessing the power of the natural healing process. Decades of research in the human world have shown that the body’s own cells and proteins, used in the normal healing process, can be collected, concentrated, and applied to orthopedic and spinal pain, often allowing patients to avoid more invasive surgical treatments¹.

Researchers have demonstrated these same principles in the context of veterinary medicine. The adult stem cells found in bone marrow can form a variety of tissues, and their purpose is to form new cartilage, bone, and connective tissue in addition to powerfully signaling their neighbor cells to control inflammation². Adult stem cells from bone marrow have been used to treat many types of injuries including suspensory ligaments, osteochondral defects, stifle joints, laminitis, other soft tissue (muscle, tendon, ligament), and bone injuries^3–10.

OUR ADVANTAGE: ENRICHED PROTEIN CONCENTRATE

When plasma is passed back and forth between B and C port syringes, proteins flow through hundreds of nanoporous fibers, causing water and salt molecules to exit the filtration system, leaving behind an enriched protein concentrate.

This enriched protein concentrate contains proteins like Interleukin-1 receptor antagonist protein (IRAP), Vascular endothelial growth factor (VEGF), Platelet-derived growth factor (PDGF), Transforming growth factor beta (TGF – beta), Fibroblast growth factors (FGF), Fibronectin and Fibrinogen, and, most importantly, Alpha-2 Macroglobulin (A2M)^11-13. A2M is a powerful natural plasma protease inhibitor, cytokine carrier, and ligand for cell-signaling receptors, and is synthesized primarily in the liver but dispersed through the blood plasma in whole blood and in bone marrow^13,14. A2M also stops the progression of osteoarthritis (OA) by preventing degenerative cartilage breakdown and assisting with cartilage repair^11,12.

WHERE DO ADULT STEM CELLS COME FROM?
In adult horses, stem cells are present within a variety of tissues and organs. Due to ease of use and decades of history and optimization, bone marrow from the sternum and iliac crest (pelvis) are the two most common sources¹⁵.

HOW ARE ADULT STEM CELLS OBTAINED AND PREPARED?
The veterinarian uses a needle to withdraw bone marrow. A trained technician then uses specifically designed equipment to concentrate the adult stem cells and growth factors in the bone marrow and returns the concentrated material for use as deemed appropriate by the veterinarian^1,4.

WILL MY HORSE REJECT THE ADULT STEM CELLS?
No, since they are cells collected from your horse’s own tissue, there is little threat of rejection².

WHAT IS THE DIFFERENCE BETWEEN CELL THERAPY AND PLATELET-RICH PLASMA (PRP) THERAPY OR IRAP?
PRP and IRAP, which both come from blood, are an indirect therapy based upon the fact that cells respond to growth factors like IRAP and the ones found in platelets. The success of any indirect therapy depends on the presence of stem cells and other cells in the environment and their ability to respond to IRAP and/ or the growth factors in PRP. In contrast, bone marrow cell therapy is a direct therapy. Within the bone marrow are adult stem cells, platelets, and growth factors. Not only does bone marrow cell therapy do the job of PRP therapy, but it also contains the active adult stem cells, which are vital to the healing process².

WHAT ABOUT THE USE OF EMBRYONIC/AMNIOTIC/CORD BLOOD STEM CELLS?
Any cell that does not come from your horse will be inferior to their own cells for one reason: they are foreign. And the immune system has a simple job: identify foreign cells/materials, and destroy them¹⁶. This is why organ transplant recipients must take anti-rejection drugs as long as they live—they have to keep their immune system from doing its job in order to keep their transplanted organ¹⁷. If a practitioner chooses to treat a patient with any cell type that is not the patient’s own cells, and that patient is not on anti-rejection drugs, the immune system will recognize the transplanted cells as foreign and clear them. Using your horse’s own cells is the only way to ensure that they will be accepted.

ART BMC VET CELL RECOVERY

The ART BMC VET is the highest level of cell recovery technology available, returning 90% of cells. The closest competitor product returns only 76%.

1. Hernigou P, Homma Y, Flouzat Lachaniette CH, et al. Benefits of small volume and small syringe for bone marrow aspirations of mesenchymal stem cells. Int Orthop. 2013;37(11):2279-2287. doi:10.1007/ s00264-013-2017-z

2. Murphy MB, Moncivais K, Caplan AI. Mesenchymal stem cells: Environmentally responsive therapeutics for regenerative medicine. Exp Mol Med. 2013;45(11):e54-16. doi:10.1038/emm.2013.94

3. Herthel DJ. Enhanced Suspensory Ligament Healing in 100 Horses by Stem Cells and Other Bone Marrow Components. Proc Am Assoc Equine Partners. 2001;47:319-321. Link.

4. Chu CR, Fortier LA, Williams A, et al. Minimally Manipulated Bone Marrow Concentrate Compared with Microfracture Treatment of Full-Thickness Chondral Defects: A One-Year Study in an Equine Model. J Bone Joint Surg Am. 2018;100(2):138-146. doi:10.2106/JBJS.17.00132

5. Angelone M, Conti V, Biacca C, et al. The contribution of adipose tissue-derived mesenchymal stem cells and platelet-rich plasma to the treatment of chronic equine laminitis: A proof of concept. Int J Mol Sci. 2017;18(10). doi:10.3390/ijms18102122

6. Carvalho A de M, Badial P, Álvarez LEC, et al. Equine tendonitis therapy using mesenchymal stem cells and platelet concentrates: a randomized controlled trial. Stem Cell Res Ther. 2013;4(4):85. doi:10.1186/scrt236

7. Black LL, Gaynor J, Gahring D, et al. Effect of adipose-derived mesenchymal stem and regenerative cells on lameness in dogs with chronic osteoarthritis of the coxofemoral joints: a randomized, double-blinded, multicenter, controlled trial. Vet Ther. 2007;8(4):272-284. doi:10.1161/CIRCULATIONAHA.105.595090

8. Hall MS, Vasey JR, Russell JW, Russell T. Use of ultrasound-guided autologous bone marrow transfer for treatment of suspensory ligament desmitis in 30 race horses (2003-2010). Aust Vet J. 2013;91(3):102-107. doi:10.1111/avj.12015

9. Bertone AL, Reisbig NA, Kilborne AH, et al. Equine Dental Pulp Connective Tissue Particles Reduced Lameness in Horses in a Controlled Clinical Trial. Front Vet Sci. 2017;4(March). doi:10.3389/fvets.2017.00031

10. Ferris DJ, Frisbie DD, Kisiday JD, et al. Clinical Outcome After Intra-Articular Administration of Bone Marrow Derived Mesenchymal Stem Cells in 33 Horses With Stifle Injury. Vet Surg. 2014;43(3):255-265. doi:10.1111/j.1532-950X.2014.12100.x

11. Murphy MB, Blashki D, Buchanan RM, et al. Adult and umbilical cord blood-derived platelet-rich plasma for mesenchymal stem cell proliferation, chemotaxis, and cryo-preservation. Biomaterials. 2012;33(21):5308-5316. doi:10.1016/j.biomaterials.2012.04.007

12. Wang S, Wei X, Zhou J, et al. Identification of α2-macroglobulin as a master inhibitor of cartilage-degrading factors that attenuates the progression of posttraumatic osteoarthritis. Arthritis Rheumatol. 2014;66(7):1843-1853. doi:10.1002/art.38576

13. Cassano JM, Kennedy JG, Ross KA, Fraser EJ, Goodale MB, Fortier LA. Bone marrow concentrate and platelet-rich plasma differ in cell distribution and interleukin 1 receptor antagonist protein concentration. Knee Surgery, Sport Traumatol Arthrosc. 2018;26(1):333-342. doi:10.1007/s00167-016-3981-9

14. Rehman AA, Ahsan H, Khan FH. Alpha-2-macroglobulin: A physiological guardian. J Cell Physiol. 2013;228(8):1665-1675. doi:10.1002/jcp.24266

15. Adams MK, Goodrich LR, Rao S, et al. Equine bone marrow-derived mesenchymal stromal cells (BMDMSCs) from the ilium and sternum: are there differences? Equine Vet J. 2013;45(3):372-375. doi:10.1111/j.2042-3306.2012.00646.x

16. Yatim KM, Lakkis FG. A Brief Journey through the Immune System. Clin J Am Soc Nephrol. 2015;10(7):1274-1281. doi:10.2215/CJN.10031014

17. Holt CD. Overview of Immunosuppressive Therapy in Solid Organ Transplantation. Anesthesiol Clin. 2017;35(3):365-380. doi:10.1016/j.anclin.2017.04.001