Leon Creaney,\u00a0SEM Physician, BUPA<\/p>\n
Dear Sir,<\/p>\n
I congratulate the IOC Consensus panel on having produced as clear a
\nsummary of the current understanding of the basic and clinical science
\nrelating to PRP as the body of published literature allows. While there
\nwas initially great hope in Sport Medicine circles that PRP would become
\nthe magic bullet for injuries, recent trials such as de Vos1, have failed
\nto provide that conclusive evidence so desired.<\/p>\n
This is not surprising. The more we learn about tissue regeneration,
\nthe more apparent it becomes how complex a process it is. Tissue
\nregeneration is not a passive phenomenon, instead it is a highly co-
\nordinated interplay of multiple cell lines at different stages of
\nmaturation. Different cellular and humoral components play their different
\nroles.
\nThe process can be likened to the repair of a collapsed building. Consider
\nmuscle injury. The initial cells on scene, due to bleeding, are platelets,
\nbut they appear to be relatively passively involved – alarm bells which
\nsequester and awaken the major players. Platelets release chemotactic
\nfactors which attract neutrophils to clear the debris2,3. However within
\n24 hours macrophages4 arrive, akin to the foreman, and it is these cells
\nthat appear to regulate the process from this point onwards. If there is
\nany ‘brains’ or ‘thinking’ to tissue repair, it would seem to be the
\nmacrophages doing it. Next come the actual builders. Fibroblasts are
\nactivated to produce a collagen infrastructure, and satellite cells, to
\nform myocytes and finally myotubes, merging to become a single strand of
\nmuscle fibre5.<\/p>\n
So where do ‘growth factors’ come into it? These proteins are simply
\nthe communications being sent between the foreman and his workers. The
\nmessages are very simple – move or stay put, divide or don’t divide, live
\nor die, make collagen etc. In biology we use the terms chemotaxis;
\nmitosis; quiescence; apoptosis and protein biosynthesis. The point is this
\n– growth factors are just the messenger molecules used by one cell to send
\nan instruction to another, they are not the person giving the orders.<\/p>\n
Unfortunately the ‘language’ of growth factors is very different to
\nEnglish. We are used, pretty much, to one word having roughly one meaning.
\nHowever growth factor ‘words’ are more like a tonal language, Mandarin. In
\nthese languages the same word can have multiple different meanings
\ndepending on how you pronounce it. In the same manner, growth factors can
\nproduce varying effects depending on their concentration, time of release,
\npoint in cell cycle and recipient cell. Thus trying to pin any one growth
\nfactor down to one particular action can be pointless – TGF-?1 is commonly
\nassociated with fibrosis 3,6,7, but it can stimulate regeneration or
\nfibrosis, chemoattraction or stasis, depending on its concentration8,
\ntarget cell, and sequence within the tissue regeneration process.<\/p>\n
Moving back to the analogy, it requires a great deal of intelligence
\nto rebuild a collapsed building. The foreman has to send and receive
\naccurate messages, at the right time, and to the right people, otherwise
\nthe building will end up with structural flaws, and will probably fall
\ndown again. Imagine if he simply threw the blueprints in the air, and
\nallowed the workers to pick up a piece each and act on what it said –
\ncomplete chaos! In the same way macrophages co-ordinate a complex
\ninterplay between themselves and fibroblasts\/satellite cells.<\/p>\n
This is where PRP has the potential to fall down. PRP has variable
\nand inconsistent content and concentration.9 There is no consensus on
\ntiming of injection. What does a random bolus injection into an injury
\nachieve? Are we sending these effector cells a clear and co-ordinated set
\nof instructions with PRP? Or are they being sent a completely confusing
\nmessage? It would seem hopelessly optimistic and na?ve to presume that we
\nare accurately reproducing biological complexity.<\/p>\n
PRP has shown promise in promoting accelerated scar tissue formation
\nin dental grafts10 and wound healing11, where regeneration of complex
\ntissue is not a goal. In Sports Medicine however, we require restoration
\nof functional tissue – contractile muscle or tendon of high tensile
\nstrength – tissue of much greater complexity. The successes in maxillo-
\nfacial applications are perhaps not analogous to these situations.<\/p>\n
Whether or not PRP is eventually proven or disproven in Sports
\nInjuries, it is nevertheless a good start. The Sports Medicine world has
\nwoken to the possibilities of regenerative medicine, and is trying to be
\nscientific in the development of novel therapies. In the future we will
\nhave improved understanding of how the complex and overlapping processes
\nof tissue regeneration12 are controlled by co-ordinating cells, stem
\ncells, effector cells and the messenger molecules that they employ, and
\nmore importantly, how to manipulate these processes for a beneficial
\neffect.<\/p>\n
References<\/p>\n
1. de Vos RA, Weir A, van Schie HTM et al. Platelet-Rich Plasma
\ninjection for Chronic Achilles Tendinopathy JAMA 2010;303(2):144-149<\/p>\n
2. Anitua E, Andia I, Ardanza B, et al. Autologous platelets as a
\nsource of proteins for healing and tissue regeneration. Thromb Haemost
\n2004;91:4-15.<\/p>\n
3. Toumi H, F’guyer S, Best T. The role of neutrophils in injury and
\nrepair following muscle stretch. J Anat 2006;208:459-470<\/p>\n
4. Chazaud B, Brigitte M, Yacoub-Youssef H et al. Dual and beneficial
\nroles of macrophages during skeletal muscle regeneration. Exerc Sport Sci
\nRev 2009;37(1):18-22<\/p>\n
5. Jarvinen TAH, Jarvinen TLN, Kaariainen M. Muscle injuries: Biology
\nand Treatment. AJSM 2005;33:745-764<\/p>\n
6. Li Y, Foster W, Deasy BM. Transforming growth factor-?1 induces
\nthe differentiation of myogenic cells into fibrotic cells in injured
\nskeletal muscle. Am J Path 2004;164(3):1007-1019<\/p>\n
7. Shen W, Li Y, Tang Y. NS-398, a Cyclooxygenase-2-specific
\ninhibitor, delays skeletal muscle healing by decreasing regeneration and
\npromoting fibrosis. Am J Path 2005;167(4):1105-1117<\/p>\n
8. Bischoff R. Chemotaxis of Skeletal muscle satellite cells. Dev Dyn
\n1997;208:505-515<\/p>\n
9. Creaney L, Hamilton B. Growth factor delivery methods in the
\nmanagement of sports injuries: the state of play. BJSM 2008;42:314-320<\/p>\n
10. Marx RE. Platelet-rich plasma: evidence to support its use. J
\nOral Maxillofac Surg 2004;62(8):1047-8<\/p>\n
11. Lacci KM, Dardik A. Platelet-rich plasma:support for its use in
\nwound healing. Yale J Biol Med 2010;83(1):1-9<\/p>\n
12. Gates CB, Karthikeyan T, Fu F, Huard J. Regenerative Medicine for
\nthe musculoskeletal system based on muscle-derived stem cell. J Am Acad
\nOrthop Surg 2008;16:68-76<\/p>\n
None declared<\/p>\n
<\/p>\n","protected":false},"excerpt":{"rendered":"
Leon Creaney,\u00a0SEM Physician, BUPA Dear Sir, I congratulate the IOC Consensus panel on having produced as clear a summary of the current understanding of the basic and clinical science relating to PRP as the body of published literature allows. While there was initially great hope in Sport Medicine circles that PRP would become the magic […]<\/p>\n