Making a New You - Growth Factors and Stem Cells

Growth factors and stem cells are being used more frequently in our practice for tendon irritations, tendinitis, and bursitis around the shoulder, knee, elbow, and ankle joints. Now, stem cells are also being directly added to our cartilage regeneration efforts.

Tendinitis is an inflammation of the tendon, the structure in your body that connects muscle to bone. Tendinitis can lead to degeneration of the collagen fibers that make up the tendon. The chronic pain that develops with tendinitis has been successfully treated with soft tissue massage, stretching, icing, and careful exercises. Occasionally, cortisone is used to diminish the pain but with some risk of tendon rupture. However, it may be possible to promote healing by providing the site of injury with a high level of growth factors. In a healing response, these growth factors would stimulate cells to produce new collagen and repair the injury.

The following are important points as of today:
Growth factors are normally released from platelets in the blood at the site of an injury. During an out-patient procedure in our office, we take 30 cc's of the patient's own blood, spin down the platelets in a centrifuge, chemically and/or physically induce them to release their growth factors, and then inject them into the site of injury.

These steps stimulate a healing response and raise the concentration of growth factors to 4 - 8 times the levels that normally circulate in the blood.

The effectiveness of this procedure is promising and still uncertain. Definitive outcome studies are underway. Studies that support the use of growth factors are referenced at the end of this article. The three key factors most commonly studied are: TGF-B (transforming growth factor-B), PDGF-AB (platelet-derived fibroblast growth factor) and bFGF (beta fibroblast growth factor). Studies on injection of these factors from the platelets in peripheral blood have focused on accelerating the healing process and reducing pain in Achilles tendon repair studies. One such study in chronic elbow tendinitis demonstrated a 93% reduction of pain.

When placed into a treated arthritic area and stimulated with motion, stem cells from adult bone marrow produce growth factors and form cells that can develop into cartilage. At The Stone Clinic, we have used the paste grafting technique for repairing arthritic cartilage in knees and ankles for the past 17 years and have recently demonstrated the percentage and activity of progenitor cells in the paste. In studies, stem cells have been shown to develop into cartilage cells and produce relevant growth factors. Further studies are underway at the Stone Research Foundation to optimize the performance of stem cells by adding additional growth factors. Paste grafting remains a key technique to biologically reconstruct injured and arthritic knees.

Stem cells, combined with full articular cartilage grafts and a transplanted meniscus allograft, represent a new method to re-build severely arthritic knees. We refer to this as "biologic knee reconstruction" rather than "bionic" or "artificial knee replacement." Biologic knee reconstruction is performed as an outpatient arthroscopic procedure and avoids some of the risks and limitations of artificial joint knees. We have recently submitted for publication our 2 - 11-year follow-up studies of the first 106 patients who have undergone our combined biologic knee reconstruction. The results show a solid 79.2% success rate with a predicted survival rate of 9.6 years.

Stay tuned for more updates and stay fit this summer.

Kevin R. Stone, M.D. and
The Team at The Stone Clinic and Stone Research Foundation

More on the latest treatment and science can be found at www.stoneresearch.org

Growth Factors and Stem Cells References

1. Alvarez RH, Kantarjian HM, Cortes JE. Biology of platelet-derived growth factor and its involvement in disease. Mayo Clin Proc. 2006;81(9):1241-1257.

2. Anitua E, Andia I, Sanchez M, Azofra J, del Mar Zalduendo M, de la Fuente M, Nurden P, Nurden AT. Autologous preparations rich in growth factors promote proliferation and induce VEGF and HGF production by human tendon cells in culture. J Orthop Res. 2005;23(2):281-286.

3. Canalis E, Centrella M, McCarthy T. Effects of basic fibroblast growth factor on bone formation in vitro. J Clin Invest. 1988;81(5):1572-1577.

4. Canalis E, McCarthy TL, Centrella M. Effects of platelet-derived growth factor on bone formation in vitro. J Cell Physiol. 1989;140(3):530-537.

5. Chan BP, Chan KM, Maffulli N, Webb S, Lee KK. Effect of basic fibroblast growth factor. An in vitro study of tendon healing. Clin Orthop Relat Res. 1997(342):239-247.

6. Creaney L, Hamilton B. Growth factor delivery methods in the management of sports injuries: the state of play. Br J Sports Med. 2008;42(5):314-320.

7. Efthimiadou A, Asimakopoulos B, Nikolettos N, Giatromanolaki A, Sivridis E, Papachristou DN, Kontoleon E. Angiogenic effect of intramuscular administration of basic and acidic fibroblast growth factor on skeletal muscles and influence of exercise on muscle angiogenesis. Br J Sports Med. 2006;40(1):35-39; discussion 35-39.

8. Everts PA, Devilee RJ, Oosterbos CJ, Mahoney CB, Schattenkerk ME, Knape JT, van Zundert A. Autologous platelet gel and fibrin sealant enhance the efficacy of total knee arthroplasty: improved range of motion, decreased length of stay and a reduced incidence of arthrofibrosis. Knee Surg Sports Traumatol Arthrosc. 2007;15(7):888-894.

9. Gruber R, Varga F, Fischer MB, Watzek G. Platelets stimulate proliferation of bone cells: involvement of platelet-derived growth factor, microparticles and membranes. Clin Oral Implants Res. 2002;13(5):529-535.

10. Kobayashi D, Kurosaka M, Yoshiya S, Mizuno K. Effect of basic fibroblast growth factor on the healing of defects in the canine anterior cruciate ligament. Knee Surg Sports Traumatol Arthrosc. 1997;5(3):189-194.

11. Menetrey J, Kasemkijwattana C, Day CS, Bosch P, Vogt M, Fu FH, Moreland MS, Huard J. Growth factors improve muscle healing in vivo. J Bone Joint Surg Br.2000;82(1):131-137.

12. Mishra A, Pavelko T. Treatment of chronic elbow tendinosis with buffered platelet-rich plasma. Am J Sports Med. 2006;34(11):1774-1778.

13. Miyazono K, Okabe T, Urabe A, Yamanaka M, Takaku F. A platelet factor that stimulates the proliferation of vascular endothelial cells. Biochem Biophys Res Commun. 1985;126(1):83-88.

14. Molloy T, Wang Y, Murrell G. The roles of growth factors in tendon and ligament healing. Sports Med. 2003;33(5):381-394.

15. Patel VR, Singh D, Calvert PT, Bayley JI. Arthroscopic subacromial decompression: results and factors affecting outcome. J Shoulder Elbow Surg. 1999;8(3):231-237.

16. Sanchez AR, Sheridan PJ, Kupp LI. Is platelet-rich plasma the perfect enhancement factor? A current review. Int J Oral Maxillofac Implants. 2003;18(1):93-103.

17. Sanchez M, Anitua E, Azofra J, Andia I, Padilla S, Mujika I. Comparison of surgically repaired Achilles tendon tears using platelet-rich fibrin matrices. Am J Sports Med. 2007;35(2):245-251.

18. ThorntonSC, Por SB, Penny R, Richter M, Shelley L, Breit SN. Identification of the major fibroblast growth factors released spontaneously in inflammatory arthritis as platelet derived growth factor and tumour necrosis factor-alpha. Clin Exp Immunol. 1991;86(1):79-86.

19. Yoshikawa Y, Abrahamsson SO. Dose-related cellular effects of platelet-derived growth factor-BB differ in various types of rabbit tendons in vitro. Acta Orthop Scand. 2001;72(3):287-292.