Treatment of Muscle Injuries by Local Administration of Autologous Conditioned Serum: Animal Experiments Using a Muscle Contusion Model

Abstract

Muscle contusions represent a major part of sports injuries. The suggested treatments are generally sufficient to support muscle healing, but require a relatively long period of time. Given that autologous blood products are safe treatments, we have used a technique which stimulates the release of certain growth factors in the autologous conditioned serum (ACS). Those growth factors are known to improve the proliferative activity of myogenic precursor cells. Mice were subjected to an experimental contusion injury to their gastrocnemius muscle; one group received local injections of ACS at 2 hrs, 24 hrs, and 48 hrs after injury, a control group received saline injections. The histology results showed that satellite cell activation at 30/48 hrs post injury was accelerated and the diameter of the regenerating myofibers was increased compared to the controls within the first week after injury. ELISA results on the ACS have shown that the elevations in FGF-2 (460 %) and TGF-β1 (82 %) could be partly responsible for the accelerating effects on regeneration due to proliferative and chemotactic properties. We conclude that ACS injection is a promising approach to reduce the time of recovery from muscle injury. In terms of clinical targets, this new approach could be used in the treatment of sports injuries and may also be interesting in postoperative situations.

Key words

Growth factors - muscle injury - regeneration - satellite cell

References

• 1 Allen R E, Boxhorn L K. Regulation of skeletal muscle satellite cell proliferation and differentiation by transforming growth factor-beta, insulin-like growth factor I, and fibroblast growth factor.  J Cell Physiol. 1989;  138 311-315
• 2 Allen R E, Dodson M V, Luiten L S. Regulation of skeletal muscle satellite cell proliferation by bovine pituitary fibroblast growth factor.  Exp Cell Res. 1984;  152 154-160
• 3 Allen R E, Sheehan S M, Taylor R G, Kendall T L, Rice G M. Hepatocyte growth factor activates quiescent skeletal muscle satellite cells in vitro.  J Cell Physiol. 1995;  165 307-312
• 4 Baird A. Fibroblast growth factors: activities and significance of non-neurotrophin neurotrophic growth factors.  Curr Opin Neurobiol. 1994;  4 78-86
• 5 Beiner J M, Jokl P. Muscle contusion injuries: current treatment options.  J Am Acad Orthop Surg. 2001;  9 227-237
• 6 Bischoff R. Chemotaxis of skeletal muscle satellite cells.  Dev Dyn. 1997;  208 505-515
• 7 Canale S T, Cantler E D, Sisk T D, Freeman B L. A chronicle of injuries of an American intercollegiate football team 3rd.  Am J Sports Med. 1981;  9 384-389
• 8 Garrett Jr W E. Muscle strain injuries.  Am J Sports Med. 1996;  24 S2-8
• 9 Garrett Jr W E. Muscle strain injuries: clinical and basic aspects.  Med Sci Sports Exerc. 1990;  22 436-443
• 10 Guinebretiere J M, Sabourin J C. Ki-67, marker of proliferation [in French].  Ann Pathol. 1997;  17 25-30
• 11 Hawke T J, Garry D J. Myogenic satellite cells: physiology to molecular biology.  J Appl Physiol. 2001;  91 534-551
• 12 Hurme T, Kalimo H. Activation of myogenic precursor cells after muscle injury.  Med Sci Sports Exerc. 1992;  24 197-205
• 13 Husmann I, Soulet L, Gautron J, Martelly I, Barritault D. Growth factors in skeletal muscle regeneration.  Cytokine Growth Factor Rev. 1996;  7 249-258
• 14 Jarvinen T A, Kaariainen M, Jarvinen M, Kalimo H. Muscle strain injuries.  Curr Opin Rheumatol. 2000;  12 155-161
• 15 Kasemkijwattana C, Menetrey J, Bosch P, Somogyi G, Moreland M S, Fu F H, Buranapanitkit B, Watkins S S, Huard J. Use of growth factors to improve muscle healing after strain injury.  Clin Orthop. 2000;  (370) 272-285
• 16 Kasemkijwattana C, Menetrey J, Somogyl G, Moreland M S, Fu F H, Buranapanitkit B, Watkins S C, Huard J. Development of approaches to improve the healing following muscle contusion.  Cell Transplant. 1998;  7 585-598
• 17 Kauhanen S, von Boguslawsky K, Michelsson J E, Leivo I. Satellite cell proliferation in rabbit hindlimb muscle following immobilization and remobilization: an immunohistochemical study using MIB 1 antibody.  Acta Neuropathol. 1998;  95 165-170
• 18 Lefaucheur J P, Sebille A. Muscle regeneration following injury can be modified in vivo by immune neutralization of basic fibroblast growth factor, transforming growth factor beta 1 or insulin-like growth factor I.  J Neuroimmunol. 1995;  57 85-91
• 19 Meijer H, Reinecke J, Becker C, Tholen G, Wehling P. The production of anti-inflammatory cytokines in whole blood by physico-chemical induction.  Inflamm Res. 2003;  52 404-407
• 20 Menetrey J, Kasemkijwattana C, Day C S, Bosch P, Vogt M, Fu F H, Moreland M S, Huard J. Growth factors improve muscle healing in vivo.  J Bone Joint Surg Br. 2000;  82 131-137
• 21 Nilsen-Hamilton M. Transforming growth factor-beta and its actions on cellular growth and differentiation.  Curr Top Dev Biol. 1990;  24 95-136
• 22 Olson E N, Sternberg E, Hu J S, Spizz G, Wilcox C. Regulation of myogenic differentiation by type beta transforming growth factor.  J Cell Biol. 1986;  103 1799-1805
• 23 Ross R, Raines E W, Bowen-Pope D F. The biology of platelet-derived growth factor.  Cell. 1986;  46 155-169
• 24 Sheehan S M, Allen R E. Skeletal muscle satellite cell proliferation in response to members of the fibroblast growth factor family and hepatocyte growth factor.  J Cell Physiol. 1999;  181 499-506
• 25 Sheehan S M, Tatsumi R, Temm-Grove C J, Allen R E. HGF is an autocrine growth factor for skeletal muscle satellite cells in vitro.  Muscle Nerve. 2000;  23 239-245
• 26 Workman P, Twentyman P, Balkwill F, Balmain A, Chaplin D, Double J, Embleton J, Newell D, Raymond R, Stables J, Stephens T, Wallace J. United Kingdom Co-ordinating Committee on Cancer Research (UKCCCR) guidelines for the welfare of animals in experimental neoplasia (Second Edition).  Br J Cancer. 1998;  77 1-10
• 27 Wright-Carpenter T, Klein P, Schäferhoff P, Appell H J, Mir L M, Wehling P. Treatment of muscle injuries by local administration of autologous conditioned serum: a pilot study on sportsmen with muscle strains.  Int J Sports Med. 2004;  25 589-594
• 28 Yablonka-Reuveni Z, Seger R, Rivera A J. Fibroblast growth factor promotes recruitment of skeletal muscle satellite cells in young and old rats.  J Histochem Cytochem. 1999;  47 23-42
• 29 Yoshida K, Gage F H. Cooperative regulation of nerve growth factor synthesis and secretion in fibroblasts and astrocytes by fibroblast growth factor and other cytokines.  Brain Res. 1992;  569 14-25