title: A new platelet cryoprecipitate glue promoting bone formation after ectopic mesenchymal stromal cell-loaded biomaterial implantation in nude mice.
abstract: BACKGROUND
  This study investigated the promising effect of a new Platelet Glue obtained from Cryoprecipitation of Apheresis Platelet products (PGCAP) used in combination with Mesenchymal Stromal Cells (MSC) loaded on ceramic biomaterials to provide novel strategies enhancing bone repair.
  
  
  METHODS
  PGCAP growth factor content was analyzed by ELISA and compared to other platelet and plasma-derived products. MSC loaded on biomaterials (65% hydroxyapatite/35% beta-TCP or 100% beta-TCP) were embedded in PGCAP and grown in presence or not of osteogenic induction medium for 21 days. Biomaterials were then implanted subcutaneously in immunodeficient mice for 28 days. Effect of PGCAP on MSC was evaluated in vitro by proliferation and osteoblastic gene expression analysis and in vivo by histology and immunohistochemistry.
  
  
  RESULTS
  We showed that PGCAP, compared to other platelet-derived products, allowed concentrating large amount of growth factors and cytokines which promoted MSC and osteoprogenitor proliferation. Next, we found that PGCAP improves the proliferation of MSC and osteogenic-induced MSC. Furthermore, we demonstrated that PGCAP up-regulates the mRNA expression of osteogenic markers (Collagen type I, Osteonectin, Osteopontin and Runx2). In vivo, type I collagen expressed in ectopic bone-like tissue was highly enhanced in biomaterials embedded in PGCAP in the absence of osteogenic pre-induction. Better results were obtained with 65% hydroxyapatite/35% beta-TCP biomaterials as compared to 100% beta-TCP.
  
  
  CONCLUSIONS
  We have demonstrated that PGCAP is able to enhance in vitro MSC proliferation, osteoblastic differentiation and in vivo bone formation in the absence of osteogenic pre-induction. This clinically adaptable platelet glue could be of interest for improving bone repair.
authors.forename: Marina
authors.initials: M
authors.lastname: Trouillas
authors.forename: Marie
authors.initials: M
authors.lastname: Prat
authors.forename: Christelle
authors.initials: C
authors.lastname: Doucet
authors.forename: Isabelle
authors.initials: I
authors.lastname: Ernou
authors.forename: Corinne
authors.initials: C
authors.lastname: Laplace-Builhé
authors.forename: Patrick Saint
authors.initials: PS
authors.lastname: Blancard
authors.forename: Xavier
authors.initials: X
authors.lastname: Holy
authors.forename: Jean-Jacques
authors.initials: JJ
authors.lastname: Lataillade
mesh_terms: D000269:Adhesives / Q000494:pharmacology; D000818:Animals; D001672:Biocompatible Materials / Q000494:pharmacology*; D015415:Biomarkers / Q000378:metabolism; D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism; D001842:Bone and Bones / Q000187:drug effects* / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D008819:Mice, Nude; D010006:Osteoblasts / Q000187:drug effects / Q000378:metabolism; D010012:Osteogenesis / Q000187:drug effects*; D012333:RNA, Messenger / Q000378:metabolism; D023822:Tissue Engineering / Q000379:methods
chemical_list: D000269:Adhesives; D001672:Biocompatible Materials; D015415:Biomarkers; D012333:RNA, Messenger