title: Determining a clinically relevant strategy for bone tissue engineering: an "all-in-one" study in nude mice.
abstract: OBJECTIVE
  Autologous bone grafting (BG) remains the standard reconstruction strategy for large craniofacial defects. Calcium phosphate (CaP) biomaterials, such as biphasic calcium phosphate (BCP), do not yield consistent results when used alone and must then be combined with cells through bone tissue engineering (BTE). In this context, total bone marrow (TBM) and bone marrow-derived mesenchymal stem cells (MSC) are the primary sources of cellular material used with biomaterials. However, several other BTE strategies exist, including the use of growth factors, various scaffolds, and MSC isolated from different tissues. Thus, clinicians might be unsure as to which method offers patients the most benefit. For this reason, the aim of this study was to compare eight clinically relevant BTE methods in an "all-in-one" study.
  
  
  METHODS
  We used a transgenic rat strain expressing green fluorescent protein (GFP), from which BG, TBM, and MSC were harvested. Progenitor cells were then mixed with CaP materials and implanted subcutaneously into nude mice. After eight weeks, bone formation was evaluated by histology and scanning electron microscopy, and GFP-expressing cells were tracked with photon fluorescence microscopy.
  
  
  CONCLUSIONS
  Bone formation was observed in only four groups. These included CaP materials mixed with BG or TBM, in which abundant de novo bone was formed, and BCP mixed with committed cells grown in two- and three-dimensions, which yielded limited bone formation. Fluorescence microscopy revealed that only the TBM and BG groups were positive for GFP expressing-cells, suggesting that these donor cells were still present in the host and contributed to the formation of bone. Since the TBM-based procedure does not require bone harvest or cell culture techniques, but provides abundant de novo bone formation, we recommend consideration of this strategy for clinical applications.
authors.affiliation: INSERM (Institut National de la Santé et de la Recherche Médicale), UMR (Unité Mixte de Recherche) 791, center for osteoarticular and dental tissue engineering, Université de Nantes, Nantes, France ; Centre Hospitalier Universitaire de Nantes, Clinique de Stomatologie et de Chirurgie maxillo-faciale, Nantes, France ; Centre Hospitalier Universitaire de Nantes, Pôle Hospitalo-Universitaire 4, Nantes, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Corre
authors.affiliation: INSERM (Institut National de la Santé et de la Recherche Médicale), UMR (Unité Mixte de Recherche) 791, center for osteoarticular and dental tissue engineering, Université de Nantes, Nantes, France ; Centre Hospitalier Universitaire de Nantes, Pôle Hospitalo-Universitaire 4, Nantes, France.
authors.forename: Christophe
authors.initials: C
authors.lastname: Merceron
authors.affiliation: INSERM (Institut National de la Santé et de la Recherche Médicale), UMR (Unité Mixte de Recherche) 791, center for osteoarticular and dental tissue engineering, Université de Nantes, Nantes, France ; Centre Hospitalier Universitaire de Nantes, Pôle Hospitalo-Universitaire 4, Nantes, France.
authors.forename: Caroline
authors.initials: C
authors.lastname: Vignes
authors.affiliation: INSERM (Institut National de la Santé et de la Recherche Médicale), UMR (Unité Mixte de Recherche) 791, center for osteoarticular and dental tissue engineering, Université de Nantes, Nantes, France ; Centre Hospitalier Universitaire de Nantes, Pôle Hospitalo-Universitaire 4, Nantes, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Sourice
authors.affiliation: INSERM (Institut National de la Santé et de la Recherche Médicale), UMR (Unité Mixte de Recherche) 791, center for osteoarticular and dental tissue engineering, Université de Nantes, Nantes, France ; Centre Hospitalier Universitaire de Nantes, Pôle Hospitalo-Universitaire 4, Nantes, France.
authors.forename: Martial
authors.initials: M
authors.lastname: Masson
authors.affiliation: INSERM (Institut National de la Santé et de la Recherche Médicale), UMR (Unité Mixte de Recherche) 791, center for osteoarticular and dental tissue engineering, Université de Nantes, Nantes, France ; Centre Hospitalier Universitaire de Nantes, Clinique d'Oto-Rhino-Laryngologie et de Chirurgie cervico-faciale, Nantes, France ; Centre Hospitalier Universitaire de Nantes, Pôle Hospitalo-Universitaire 4, Nantes, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Durand
authors.affiliation: INSERM (Institut National de la Santé et de la Recherche Médicale), UMR (Unité Mixte de Recherche) 791, center for osteoarticular and dental tissue engineering, Université de Nantes, Nantes, France ; Centre Hospitalier Universitaire de Nantes, Clinique d'Oto-Rhino-Laryngologie et de Chirurgie cervico-faciale, Nantes, France ; Centre Hospitalier Universitaire de Nantes, Pôle Hospitalo-Universitaire 4, Nantes, France.
authors.forename: Florent
authors.initials: F
authors.lastname: Espitalier
authors.affiliation: INSERM (Institut National de la Santé et de la Recherche Médicale), UMR (Unité Mixte de Recherche) 791, center for osteoarticular and dental tissue engineering, Université de Nantes, Nantes, France ; Centre Hospitalier Universitaire de Nantes, Pôle Hospitalo-Universitaire 4, Nantes, France.
authors.forename: Paul
authors.initials: P
authors.lastname: Pilet
authors.affiliation: INSERM (Institut National de la Santé et de la Recherche Médicale), UMR (Unité Mixte de Recherche) 791, center for osteoarticular and dental tissue engineering, Université de Nantes, Nantes, France ; Centre Hospitalier Universitaire de Nantes, Pôle Hospitalo-Universitaire 4, Nantes, France.
authors.forename: Thomas
authors.initials: T
authors.lastname: Cordonnier
authors.affiliation: Centre Hospitalier Universitaire de Nantes, Clinique de Stomatologie et de Chirurgie maxillo-faciale, Nantes, France ; Centre Hospitalier Universitaire de Nantes, Pôle Hospitalo-Universitaire 4, Nantes, France.
authors.forename: Jacques
authors.initials: J
authors.lastname: Mercier
authors.affiliation: INSERM, UMR 1064, Centre pour la recherche en transplantation et immunologie et Plate-forme Transgenic Rats Nantes, Institut de Transplantation Urologie-Néphrologie (ITUN), Nantes, France.
authors.forename: Séverine
authors.initials: S
authors.lastname: Remy
authors.affiliation: INSERM, UMR 1064, Centre pour la recherche en transplantation et immunologie et Plate-forme Transgenic Rats Nantes, Institut de Transplantation Urologie-Néphrologie (ITUN), Nantes, France.
authors.forename: Ignacio
authors.initials: I
authors.lastname: Anegon
authors.affiliation: INSERM (Institut National de la Santé et de la Recherche Médicale), UMR (Unité Mixte de Recherche) 791, center for osteoarticular and dental tissue engineering, Université de Nantes, Nantes, France ; Centre Hospitalier Universitaire de Nantes, Pôle Hospitalo-Universitaire 4, Nantes, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Weiss
authors.affiliation: INSERM (Institut National de la Santé et de la Recherche Médicale), UMR (Unité Mixte de Recherche) 791, center for osteoarticular and dental tissue engineering, Université de Nantes, Nantes, France ; Centre Hospitalier Universitaire de Nantes, Pôle Hospitalo-Universitaire 4, Nantes, France.
authors.forename: Jérôme
authors.initials: J
authors.lastname: Guicheux
mesh_terms: D000818:Animals; D001853:Bone Marrow / Q000502:physiology*; D016026:Bone Marrow Transplantation; D001861:Bone Regeneration / Q000502:physiology*; D001842:Bone and Bones; D058948:Cell Tracking; D005260:Female; D015870:Gene Expression; D017930:Genes, Reporter; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006882:Hydroxyapatites / Q000378:metabolism; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000502:physiology*; D051379:Mice; D008819:Mice, Nude; D010012:Osteogenesis / Q000502:physiology*; D051381:Rats; D012867:Skin; D023822:Tissue Engineering / Q000379:methods*; D054457:Tissue Scaffolds; D014183:Transplantation, Heterologous
chemical_list: D006882:Hydroxyapatites; C074950:hydroxyapatite-beta tricalcium phosphate; D049452:Green Fluorescent Proteins