title: First-in-human study and clinical case reports of the alveolar bone regeneration with the secretome from human mesenchymal stem cells.
abstract: BACKGROUND
  Secreted growth factors and cytokines in the conditioned medium from bone marrow-derived mesenchymal stem cells (MSC-CM) have several effects on cell behavior. Our previous studies revealed that MSC-CM enhances bone regeneration by increasing cell mobilization, angiogenesis, and osteogenesis in vitro and in vivo. This clinical study was undertaken to evaluate the safety and use of MSC-CM for alveolar bone regeneration in eight patients who were diagnosed as needing bone augmentation prior to dental implant placement.
  
  
  METHODS
  The protocol of this clinical study was approved by the ethics committee of Nagoya University Hospital. MSC-CM was prepared from conditioned medium from commercially available human bone marrow-derived MSCs. Patients were treated with beta-tricalcium phosphate (β-TCP) or an atelocollagen sponge soaked with MSC-CM. Clinical and radiographic assessments were performed during the follow-up period. Histological assessments were also performed in some cases. Clinical and histological data from patients who underwent the SFE procedure without MSC-CM were also used retrospectively as reference controls.
  
  
  RESULTS
  MSC-CM contained several cytokines such as insulin-like growth factor-1, vascular endothelial growth factor, transforming growth factor-β1, and hepatocyte growth factor in relatively low amounts. No systemic or local complications were reported throughout the study. Radiographic evaluation revealed early bone formation in all cases. Histological evaluation also supported the radiographic findings. Furthermore, infiltration of inflammatory cells was scarce throughout the specimens.
  
  
  CONCLUSIONS
  MSC-CM was used safely and with less inflammatory signs and appears to have great osteogenic potential for regenerative medicine of bone. This is the first in-human clinical study of alveolar bone regeneration using MSC-CM.
authors.affiliation: Department of Oral and Maxillofacial Surgery, Nagoya University Graduate School of Medicine, 65 Tsuruma-cho, Showa-ku, Nagoya, 466-8550, Japan. w-kat@med.nagoya-u.ac.jp.
authors.forename: Wataru
authors.initials: W
authors.lastname: Katagiri
authors.affiliation: Department of Oral and Maxillofacial Surgery, Nagoya University Graduate School of Medicine, 65 Tsuruma-cho, Showa-ku, Nagoya, 466-8550, Japan.
authors.forename: Masashi
authors.initials: M
authors.lastname: Osugi
authors.affiliation: Department of Oral and Maxillofacial Surgery, Nagoya University Graduate School of Medicine, 65 Tsuruma-cho, Showa-ku, Nagoya, 466-8550, Japan.
authors.forename: Takamasa
authors.initials: T
authors.lastname: Kawai
authors.affiliation: Department of Oral and Maxillofacial Surgery, Nagoya University Graduate School of Medicine, 65 Tsuruma-cho, Showa-ku, Nagoya, 466-8550, Japan.
authors.forename: Hideharu
authors.initials: H
authors.lastname: Hibi
mesh_terms: D000368:Aged; D000539:Alveolar Process / Q000473:pathology*; D000540:Alveolar Ridge Augmentation / Q000379:methods*; D001706:Biopsy; D001861:Bone Regeneration; D002478:Cells, Cultured; D003758:Dental Implantation, Endosseous / Q000379:methods*; D015921:Dental Implants; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D048091:Guided Tissue Regeneration / Q000379:methods*; D006801:Humans; D007576:Jaw, Edentulous, Partially / Q000473:pathology / Q000601:surgery; D008297:Male; D008567:Membranes, Artificial; D008875:Middle Aged; D018579:Patient Selection; D010518:Periodontitis / Q000150:complications; D011862:Radiography, Panoramic; D013524:Surgical Flaps; D054457:Tissue Scaffolds; D014057:Tomography, X-Ray Computed; D016896:Treatment Outcome
chemical_list: D015921:Dental Implants; D008567:Membranes, Artificial