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Le nuove frontiere della medicina rigenerativa I SISTEMI AUTOMATIZZATI Biella, 5 giugno 2009 Biella, 5 giugno 2009 Platelets play an important role in mechanisms of tissue repair Biella, 5 giugno 2009 Platelets Anucleated cells derived from fragments of megakaryocites Normal value in peripheral blood:150-400x103/uL Half life in peripheral blood: 8-10 days Biella, 5 giugno 2009 Platelets contain granules that act as repairing factors receptorial mechanisms PDGF (Platelet derived growth factor): – mitogenic and angiogenic – up-regolation of different ripairing factors Biella, 5 giugno 2009 Platelets contain granules that act as repairing factors receptorial mechanisms TGF- (Transforming growth factor beta): – Fibroblasts and pre-osteoblasts stimulation, – Inhibition of bone reabsortion – chemotaxis Biella, 5 giugno 2009 Platelets contain granules that act as repairing factors receptorial mechanisms EGF (Epidermal growth factor): Mesenchimal and epidermal cell stimulation VEGF (Vascular endothelial growth factor): Endothelial cell stimulation IGF I-II (Insulin like factors): Osteoblasts increment Stimulation of bone deposition Biella, 5 giugno 2009 Recombinant PDGFs Natural PDGFs •Engineered growth factor Autologous Allogeneic •(Bone Morphogenetic Proteins) •OP-1- BMP7 (Osteogenic Protein-1) •BMP-2 ( InductOs ) •rhBMP-2(INFUSETM) •rhPDGF BB (Regranex) ? Biella, 5 giugno 2009 Natural PDGFs: topical use Autologous Allogeneic Biella, 5 giugno 2009 Platelet gel: a new blood component PRP and PPP Platelet aggregates and fibrin glue Biella, 5 giugno 2009 Platelet gel Manual Automatic preparation Biella, 5 giugno 2009 Platelet gel Automatic method – – – – Asepsis Reproducibility High speed Real time availability – Costs? Manual method – Risk of contamination – Operator dependent – Time consuming – Costs? Biella, 5 giugno 2009 Automatic method (1) Lost of platelets during manipulation High variation in growth factors concentration Small volume of blood required (27 – 110 ml) High efficiency in collecting and concentrating platelets Biella, 5 giugno 2009 Automatic method (2) High platelet recovery during manipulation Live platelets No leucocyte degranulation (low levels of MPO) Antimicrobial properties of Platelet Gel at the site of application (with low levels of MPO) Biella, 5 giugno 2009 Automatic method (3) High variation in growth factor concentration The content of growth factors in PRP can vary, depending on the system used for the preparation Biella, 5 giugno 2009 Automatic technique (1) Biella, 5 giugno 2009 Automatic technique (2) Biella, 5 giugno 2009 Preparazione del PRP Preparazione del crioprecipitato ricalcificato Unione del crioprecipitato ricalcificato e del PRP Gel piastrinico Biella, 5 giugno 2009 Platelet gel Drug delivery system Biella, 5 giugno 2009 Indications of growth factors in upper limb traumatology Any time you need an accellerated repair process under strict controlled trials Biella, 5 giugno 2009 Factors influencing PDGFs levels WBC Circulating plasmatic growth factors Fibrin clot and PDGFs incorporation Adequate platelet activation Biella, 5 giugno 2009 PDGFs natural vs recombinant Autologous product All factors administered Relatively low costs Exogenous product (autoimmunity, tissue degeneration) Side effects (fever,infections,pain, amilasemia) Only one factor administered Very high costs Biella, 5 giugno 2009 Auto vs Allo Autologous Allogeneic patient’s own tissue no immune response donor priming immune response No Ethical Concerns - Less Manipulation - less risk less time less cost Ethical Concerns • More manipulation - Biella, 5 giugno 2009 more risk more time more cost Platelet gel: problems Optimal dose Randomized clinical trials Role of contaminant WBC Fresh vs frozen gel Biella, 5 giugno 2009 FUTURE GOALS PDGFs + Mesenchimal stem cells Biella, 5 giugno 2009 Fondazione IRCCS Policlinico S.Matteo – Pavia Servizio di Immunoemaologia e Trasfusionale Cesare Perotti Gianluca Viarengo Claudia Del Fante Paola Bergamaschi Andrea Marchesi Valeria Genovese Bina Romano Laura Salvaneschi Biella, 5 giugno 2009