Abstract
Skeletal muscle injuries are common causes of severe long-term pain and physical disability, accounting for up to 55% of all sports injuries. The phases of the healing processes after direct or indirect muscle injury are complex but clearly defined and include well-coordinated steps: degeneration, inflammation, regeneration, and fibrosis. Despite this frequent occurrence and the presence of a body of data on the pathophysiology of muscle injuries, none of the current treatment strategies have been shown to be really effective in strictly controlled trials. Various strategies, including standard protocol as PRICE/POLICE, fisiochinesiterapic treatment, kinesiotaping, mechanical stimulation, growth factor injections, transplantation of muscle stem cells in combination or not with biological scaffolds, and anti-fibrotic therapies, may become therapeutic alternatives to improve functional muscle recovery.
Keywords
- Vascular Endothelial Growth Factor
- Hepatocyte Growth Factor
- Satellite Cell
- Muscle Injury
- Muscle Regeneration
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.
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References
Abat F, Valles SL, Gelber PE, Polidori F, Jorda A, Garcia-Herreros S, Monllau JC, Sanchez-Ibanez JM (2015) An experimental study of muscular injury repair in a mouse model of notexin-induced lesion with EPI(R) technique. BMC Sports Sci Med Rehabil 7:7. doi:10.1186/s13102-015-0002-0
Anderson JE (2016) Hepatocyte growth factor and satellite cell activation. Adv Exp Med Biol 900:1–25. doi:10.1007/978-3-319-27511-6_1
Beiner JM, Jokl P, Cholewicki J, Panjabi MM (1999) The effect of anabolic steroids and corticosteroids on healing of muscle contusion injury. Am J Sports Med 27(1):2–9
Bleakley C M, Glasgow P, MacAuley DC (2012) PRICE needs updating, should we call the POLICE? Br J Sports Med 46:220–221. doi:10.1136/bjsports-2011-090297. Originally published online September 7, 2011
Boldrin L, Elvassore N, Malerba A, Flaibani M, Cimetta E, Piccoli M, Baroni MD, Gazzola MV, Messina C, Gamba P, Vitiello L, de Coppi P (2007) Satellite cells delivered by micro-patterned scaffolds: a new strategy for cell transplantation in muscle diseases. Tissue Eng 13(2):253–262
Borselli C, Storrie H, Benesch-Lee F, Shvartsman D, Cezar C, Lichtman JW, Vandenburgh HH, Mooney DJ (2010) Functional muscle regeneration with combined delivery of angiogenesis and myogenesis factors. Proc Natl Acad Sci U S A 107(8):3287–3292. doi:10.1073/pnas.0903875106
Borselli C, Cezar CA, Shvartsman D, Vandenburgh HH, Mooney DJ (2011) The role of multifunctional delivery scaffold in the ability of cultured myoblasts to promote muscle regeneration. Biomaterials 32(34):8905–8914. doi:10.1016/j.biomaterials.2011.08.019
Cezar CA, Roche ET, Vandenburgh HH, Duda GN, Walsh CJ, Mooney DJ (2016) Biologic-free mechanically induced muscle regeneration. Proc Natl Acad Sci U S A 113(6):1534–1539. doi:10.1073/pnas.1517517113
Chan YS, Li Y, Foster W, Horaguchi T, Somogyi G, Fu FH, Huard J (2003) Antifibrotic effects of suramin in injured skeletal muscle after laceration. J Appl Physiol 95(2):771–780. doi:10.1152/japplphysiol.00915.2002
Cianforlini M, Mattioli-Belmonte M, Manzotti S, Chiurazzi E, Piani M, Orlando F, Provinciali M, Gigante A (2015) Effect of platelet rich plasma concentration on skeletal muscle regeneration: an experimental study. J Biol Regul Homeost Agents 29(4 Suppl):47–55
Collins CA (2006) Satellite cell self-renewal. Curr Opin Pharmacol 6(3):301–306
Darby IA, Zakuan N, Billet F, Desmouliere A (2016) The myofibroblast, a key cell in normal and pathological tissue repair. Cell Mol Life Sci 73(6):1145–1157. doi:10.1007/s00018-015-2110-0
Deasy BM, Feduska JM, Payne TR, Li Y, Ambrosio F, Huard J (2009) Effect of VEGF on the regenerative capacity of muscle stem cells in dystrophic skeletal muscle. Mol Ther 17(10):1788–1798. doi:10.1038/mt.2009.136
Desmouliere A, Gabbiani G (1995) Myofibroblast differentiation during fibrosis. Exp Nephrol 3(2):134–139
Dhawan J, Rando TA (2005) Stem cells in postnatal myogenesis: molecular mechanisms of satellite cell quiescence, activation and replenishment. Trends Cell Biol 15(12):666–673
Dumont NA, Bentzinger CF, Sincennes MC, Rudnicki MA (2015) Satellite cells and skeletal muscle regeneration. Compr Physiol 5(3):1027–1059. doi:10.1002/cphy.c140068
Engebretsen L, Steffen K, Alsousou J, Anitua E, Bachl N, Devilee R, Everts P, Hamilton B, Huard J, Jenoure P, Kelberine F, Kon E, Maffulli N, Matheson G, Mei-Dan O, Menetrey J, Philippon M, Randelli P, Schamasch P, Schwellnus M, Vernec A, Verrall G (2010) IOC consensus paper on the use of platelet-rich plasma in sports medicine. Br J Sports Med 44(15):1072–1081. doi:10.1136/bjsm.2010.079822
Engert JC, Berglund EB, Rosenthal N (1996) Proliferation precedes differentiation in IGF-I-stimulated myogenesis. J Cell Biol 135(2):431–440
Engler AJ, Sen S, Sweeney HL, Discher DE (2006) Matrix elasticity directs stem cell lineage specification. Cell 126(4):677–689. doi:10.1016/j.cell.2006.06.044
Foster W, Li Y, Usas A, Somogyi G, Huard J (2003) Gamma interferon as an antifibrosis agent in skeletal muscle. J Orthop Res 21(5):798–804
Fukushima K, Badlani N, Usas A, Riano F, Fu F, Huard J (2001) The use of an antifibrosis agent to improve muscle recovery after laceration. Am J Sports Med 29(4):394–402
Gigante A, Del Torto M, Manzotti S et al (2012) Platelet rich fibrin matrix effects on skeletal muscle lesions: an experimental study. J Biol Regul Homeost Agents 26:475–484
Gigante A, Cianforlini M, Manzotti S, Ulisse S (2014) The effects of growth factors on skeletal muscle lesions. Joints 1(4):180–186
Gilbert PM, Havenstrite KL, Magnusson KE, Sacco A, Leonardi NA, Kraft P, Nguyen NK, Thrun S, Lutolf MP, Blau HM (2010) Substrate elasticity regulates skeletal muscle stem cell self-renewal in culture. Science 329(5995):1078–1081. doi:10.1126/science.1191035
Hamid MS, Yusof A, Ali MRM (2014) Platelet-rich plasma (PRP) for acute muscle injury: a systematic review. PLoS One 9(2):e90538. doi:10.1371/journal.pone.0090538
Hammond JW, Hinton RY, Curl LA, Muriel JM, Lovering RM (2009) Use of autologous platelet-rich plasma to treat muscle strain injuries. Am J Sports Med 37(6):1135–1142. doi:10.1177/0363546508330974
Huard J, Li Y, Fu FH (2002) Muscle injuries and repair: current trends in research. J Bone Joint Surg Am 84-A(5):822–832
Hurme T, Kalimo H (1992) Activation of myogenic precursor cells after muscle injury. Med Sci Sports Exerc 24(2):197–205
Hwang OK, Park JK, Lee EJ, Lee EM, Kim AY, Jeong KS (2016) Therapeutic effect of losartan, an angiotensin II type 1 receptor antagonist, on CCl4-induced skeletal muscle injury. Int J Mol Sci 17(2):227
Järvinen TA, Järvinen TL, Kääriäinen M et al (2007) Muscle injuries: optimising recovery. Best Pract Res Clin Rheumatol 21(2):317–331. pmid:17512485
Jeon OH, Elisseeff J (2016) Orthopedic tissue regeneration: cells, scaffolds, and small molecules. Drug Deliv Transl Res 6(2):105–120. doi:10.1007/s13346-015-0266-7
Kobayashi M, Ota S, Terada S, Kawakami Y, Otsuka T, Fu FH, Huard J (2016) The combined use of losartan and muscle-derived stem cells significantly improves the functional recovery of muscle in a young mouse model of contusion injuries. Am J Sports Med 44(12):3252–3261. doi:10.1177/0363546516656823
Law PK, Bertorini TE, Goodwin TG, Chen M, Fang QW, Li HJ, Kirby DS, Florendo JA, Herrod HG, Golden GS (1990) Dystrophin production induced by myoblast transfer therapy in Duchenne muscular dystrophy. Lancet 336(8707):114–115
Lee C, Fukushima K, Usas A, Xin L, Pelinkovic D, Martinek V, Huard J (2000) Biological intervention based on cell and gene therapy to improve muscle healing after laceration. J Musculoskelet Res 4(4):256–277
Lehto M, Sims TJ, Bailey AJ (1985) Skeletal muscle injury–molecular changes in the collagen during healing. Res Exp Med 185(2):95–106
Li Y, Li J, Zhu J, Sun B, Branca M, Tang Y, Foster W, Xiao X, Huard J (2007) Decorin gene transfer promotes muscle cell differentiation and muscle regeneration. Mol Ther 15(9):1616–1622. doi:10.1038/sj.mt.6300250
Li H, Hicks JJ, Wang L, Oyster N, Philippon MJ, Hurwitz S et al (2016) Customized platelet-rich plasma with transforming growth factor β1 neutralization antibody to reduce fibrosis in skeletal muscle. Biomaterials 87:147–156
Lipton BH, Schultz E (1979) Developmental fate of skeletal muscle satellite cells. Science 205(4412):1292–1294
Mann CJ, Perdiguero E, Kharraz Y, Aguilar S, Pessina P, Serrano AL, Munoz-Canoves P (2011) Aberrant repair and fibrosis development in skeletal muscle. Skelet Muscle 1(1):21. doi:10.1186/2044-5040-1-21
McLennan IS (1996) Degenerating and regenerating skeletal muscles contain several subpopulations of macrophages with distinct spatial and temporal distributions. J Anat 188(Pt 1):17–28
Mendell JR, Kissel JT, Amato AA, King W, Signore L, Prior TW, Sahenk Z, Benson S, McAndrew PE, Rice R, Nagaraja H, Stephens R, Lantry L, Morris GE, Burghes AH (1995) Myoblast transfer in the treatment of Duchenne’s muscular dystrophy. N Engl J Med 333(13):832–838
Menetrey J, Kasemkijwattana C, Day CS, Bosch P, Vogt M, Fu FH, Moreland MS, Huard J (2000) Growth factors improve muscle healing in vivo. J Bone Joint Surg [Br] 82-B:131–137. pmid:10697329
Meng J, Chun S, Asfahani R, Lochmuller H, Muntoni F, Morgan J (2014) Human skeletal muscle-derived CD133(+) cells form functional satellite cells after intramuscular transplantation in immunodeficient host mice. Mol Ther 22(5):1008–1017. doi:10.1038/mt.2014.26
Miller KJ, Thaloor D, Matteson S, Pavlath GK (2000) Hepatocyte growth factor affects satellite cell activation and differentiation in regenerating skeletal muscle. Am J Physiol Cell Physiol 278(1):C174–C181
Munoz-Canoves P, Serrano AL (2015) Macrophages decide between regeneration and fibrosis in muscle. Trends Endocrinol Metab 26(9):449–450. doi:10.1016/j.tem.2015.07.005
Oak NR, Gumucio JP, Flood MD, Saripalli AL, Davis ME, Harning JA et al (2014) Inhibition of 5-LOX, COX-1, and COX-2 increases tendon healing and reduces muscle fibrosis and lipid accumulation after rotator cuff repair. Am J Sports Med 42(12):2860–2868
Park JK, Ki MR, Lee EM, Kim AY, You SY, Han SY, Lee EJ, Hong IH, Kwon SH, Kim SJ, Rando TA, Jeong KS (2012) Losartan improves adipose tissue-derived stem cell niche by inhibiting transforming growth factor-beta and fibrosis in skeletal muscle injury. Cell Transplant 21(11):2407–2424. doi:10.3727/096368912X637055
Partridge TA, Morgan JE, Coulton GR, Hoffman EP, Kunkel LM (1989) Conversion of mdx myofibres from dystrophin-negative to -positive by injection of normal myoblasts. Nature 337(6203):176–179
Proto JD, Tang Y, Lu A, Chen WC, Stahl E, Poddar M, Beckman SA, Robbins PD, Nidernhofer LJ, Imbrogno K, Hannigan T, Mars WM, Wang B, Huard J (2015) NF-kappaB inhibition reveals a novel role for HGF during skeletal muscle repair. Cell Death Dis 6:e1730. doi:10.1038/cddis.2015.66
Relaix F, Zammit PS (2012) Satellite cells are essential for skeletal muscle regeneration: the cell on the edge returns centre stage. Development 139(16):2845–2856. doi:10.1242/dev.069088
Reurink G, Goudswaard GJ, Moen MH, Weir A, Verhaar JA, Bierma-Zeinstra SM, Maas M, Tol JL, Dutch Hamstring Injection Therapy Study I (2014) Platelet-rich plasma injections in acute muscle injury. N Engl J Med 370(26):2546–2547. doi:10.1056/NEJMc1402340
Reurink G, Goudswaard GJ, Moen MH, Weir A, Verhaar JA, Bierma-Zeinstra SM, Maas M, Tol JL, Dutch HITsI (2015) Rationale, secondary outcome scores and 1-year follow-up of a randomised trial of platelet-rich plasma injections in acute hamstring muscle injury: the Dutch Hamstring Injection Therapy study. Br J Sports Med 49(18):1206–1212. doi:10.1136/bjsports-2014-094250
Rocheteau P, Vinet M, Chretien F (2015) Dormancy and quiescence of skeletal muscle stem cells. Results Probl Cell Differ 56:215–235. doi:10.1007/978-3-662-44608-9_10
Sallay PI, Friedman RL, Coogan PG, Garrett WE (1996) Hamstring muscle injuries among water skiers: functional outcome and prevention. Am J Sports Med 24:130–136
Sambasivan R, Yao R, Kissenpfennig A, Van Wittenberghe L, Paldi A, Gayraud-Morel B, Guenou H, Malissen B, Tajbakhsh S, Galy A (2011) Pax7-expressing satellite cells are indispensable for adult skeletal muscle regeneration. Development 138(17):3647–3656. doi:10.1242/dev.067587
Sampaolesi M, Blot S, D’Antona G, Granger N, Tonlorenzi R, Innocenzi A, Mognol P, Thibaud JL, Galvez BG, Barthelemy I, Perani L, Mantero S, Guttinger M, Pansarasa O, Rinaldi C, De Angelis MGC, Torrente Y, Bordignon C, Bottinelli R, Cossu G (2006) Mesoangioblast stem cells ameliorate muscle function in dystrophic dogs. Nature 444(7119):574–579
Schiaffino S, Mammucari C (2011) Regulation of skeletal muscle growth by the IGF1-Akt/PKB pathway: insights from genetic models. Skelet Muscle 1(1):4. doi:10.1186/2044-5040-1-4
Sheehan SM, Tatsumi R, Temm-Grove CJ, Allen RE (2000) HGF is an autocrine growth factor for skeletal muscle satellite cells in vitro. Muscle Nerve 23(2):239–245
Sicari BM, Rubin JP, Dearth CL, Wolf MT, Ambrosio F, Boninger M et al (2014) An acellular biologic scaffold promotes skeletal muscle formation in mice and humans with volumetric muscle loss. Sci Transl Med 6(234):234ra58–234ra58
Skuk D, Goulet M, Roy B, Piette V, Cote CH, Chapdelaine P, Hogrel JY, Paradis M, Bouchard JP, Sylvain M, Lachance JG, Tremblay JP (2007) First test of a “high-density injection” protocol for myogenic cell transplantation throughout large volumes of muscles in a Duchenne muscular dystrophy patient: eighteen months follow-up. Neuromuscul Disord 17(1):38–46. doi:10.1016/j.nmd.2006.10.003
Taniguti AP, Pertille A, Matsumura CY, Santo Neto H, Marques MJ (2011) Prevention of muscle fibrosis and myonecrosis in mdx mice by suramin, a TGF-beta1 blocker. Muscle Nerve 43(1):82–87. doi:10.1002/mus.21869
Tedesco FS, Cossu G (2012) Stem cell therapies for muscle disorders. Curr Opin Neurol 25(5):597–603. doi:10.1097/WCO.0b013e328357f288
Terada S, Ota S, Kobayashi M, Kobayashi T, Mifune Y, Takayama K, Witt M, Vadala G, Oyster N, Otsuka T, Fu FH, Huard J (2013) Use of an antifibrotic agent improves the effect of platelet-rich plasma on muscle healing after injury. J Bone Joint Surg Am 95(11):980–988. doi:10.2106/JBJS.L.00266
Tidball JG (1995) Inflammatory cell response to acute muscle injury. Med Sci Sports Exerc 27(7):1022–1032
Toumi H, Best TM (2003) The inflammatory response: friend or enemy for muscle injury? Br J Sports Med 37(4):284–286
Visser LC, Arnoczky SP, Caballero O et al (2010) Platelet-rich fibrin constructs elute higher concentrations of transforming growth factor-β1 and increase tendon cell proliferation over time when compared to blood clots: a comparative in vitro analysis. Vet Surg 39:811–817
Wolf MT, Daly KA, Reing JE, Badylak SF (2012) Biologic scaffold composed of skeletal muscle extracellular matrix. Biomaterials 33(10):2916–2925
Würgler-Hauri CC et al (2007) Temporal expression of 8 growth factors in tendon-to-bone healing in a rat supraspinatus model. J Shoulder Elb Surg 16(5):S198–S203
Zhao W, Lu H, Wang X, Ransohoff RM, Zhou L (2016) CX3CR1 deficiency delays acute skeletal muscle injury repair by impairing macrophage functions. FASEB J 30(1):380–393. doi:10.1096/fj.14-270090
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Cianforlini, M., Coppa, V., Grassi, M., Gigante, A. (2017). New Strategies for Muscular Repair and Regeneration. In: Canata, G., d'Hooghe, P., Hunt, K. (eds) Muscle and Tendon Injuries. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-662-54184-5_14
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