title: Adipose-derived stem cells and platelet-rich plasma for preventive treatment of bisphosphonate-related osteonecrosis of the jaw in a murine model.
abstract: OBJECTIVE
  The main challenge in treating bisphosphonate-related osteonecrosis of the jaw (BRONJ) is the absence of an effective established treatment. We aimed to compare different potentially preventive treatments for BRONJ after dental extractions in zoledronic acid (ZA)-treated animals. We studied the local application of different combinations of adipose-derived stem cells (ASCs) with or without previous stimulation with bone morphogenetic protein 2 (BMP-2) and platelet-rich plasma (PRP) in rats.
  
  
  METHODS
  Fifty-six male Wistar rats were treated with ZA for 9 weeks. Dental extractions were performed in the eighth week, and the animals were divided into 4 groups. In group 1 (n = 14), alveolar coverage with mucoperiosteal flap was performed. In group 2 (n = 14), PRP was applied over the sockets and covered with the flap. In group 3 (n = 15), allogeneic ASCs with PRP were applied and covered with the flap. In group 4 (n = 13), animals were treated with ASCs cultured with BMP-2, PRP, and flap coverage. Histologic, fluorescence, and radiologic studies of the maxillae were performed.
  
  
  RESULTS
  ASC-treated animals showed lower frequency of osteonecrosis (14% vs 50%, p = 0.007) and greater bone turnover (p = 0.024) and osteoclast count (p = 0.045) than those not receiving the ASC treatment.
  
  
  CONCLUSIONS
  In this high-risk model, ASC-based treatments seem to prevent BRONJ more effectively than mucosal flap with or without PRP. The combination of ASCs and PRP appears to be synergistic, and the addition of BMP-2 could further improve the results.
authors.affiliation: Department of Oral and Maxillofacial Surgery (Head: Miguel Burgueño), Hospital Universitario La Paz, Paseo de la Castellana 261, 28046 Madrid, Spain. Electronic address: p.barba.recreo@gmail.com.
authors.forename: Paula
authors.initials: P
authors.lastname: Barba-Recreo
authors.affiliation: Department of Oral and Maxillofacial Surgery (Head: Miguel Burgueño), Hospital Universitario La Paz, Paseo de la Castellana 261, 28046 Madrid, Spain.
authors.forename: Jose Luis
authors.initials: JL
authors.lastname: Del Castillo Pardo de Vera
authors.affiliation: Cell Therapy Laboratory (Head: Damián García Olmo), Instituto de Investigación Sanitario Fundación Jiménez Díaz, Avda. Reyes Católicos 2, 28040 Madrid, Spain; Department of General Surgery, Hospital Universitario Fundación Jiménez Díaz, Avda. Reyes Católicos 2, 28040 Madrid, Spain.
authors.forename: Tihomir
authors.initials: T
authors.lastname: Georgiev-Hristov
authors.affiliation: Department of Pathology, Hospital Universitario La Paz, Paseo de la Castellana 261, 28046 Madrid, Spain.
authors.forename: Elena
authors.initials: E
authors.lastname: Ruiz Bravo-Burguillos
authors.affiliation: Cellular Biotechnology Unit, Instituto de Salud Carlos III, Carretera Majadahonda-Pozuelo km 2.200, 28220 Majadahonda, Spain; Haematopoietic Stem Cell Laboratory, Cancer Research UK, 44 Lincoln's Inn Fields, London WC2A 3LY, United Kingdom.
authors.forename: Ander
authors.initials: A
authors.lastname: Abarrategi
authors.affiliation: Department of Oral and Maxillofacial Surgery (Head: Miguel Burgueño), Hospital Universitario La Paz, Paseo de la Castellana 261, 28046 Madrid, Spain; Department of Surgery, Faculty of Medicine, Universidad Autónoma de Madrid, C/ Arzobispo Morcillo s/n, 28029 Madrid, Spain.
authors.forename: Miguel
authors.initials: M
authors.lastname: Burgueño
authors.affiliation: Cell Therapy Laboratory (Head: Damián García Olmo), Instituto de Investigación Sanitario Fundación Jiménez Díaz, Avda. Reyes Católicos 2, 28040 Madrid, Spain; Department of Surgery, Faculty of Medicine, Universidad Autónoma de Madrid, C/ Arzobispo Morcillo s/n, 28029 Madrid, Spain.
authors.forename: Mariano
authors.initials: M
authors.lastname: García-Arranz
mesh_terms: D017667:Adipocytes; D000818:Animals; D059266:Bisphosphonate-Associated Osteonecrosis of the Jaw / Q000517:prevention & control / Q000628:therapy*; D050071:Bone Density Conservation Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D004164:Diphosphonates / Q000008:administration & dosage / Q000627:therapeutic use*; D004195:Disease Models, Animal; D007093:Imidazoles / Q000008:administration & dosage / Q000627:therapeutic use*; D008297:Male; D053657:Platelet-Rich Plasma / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D013234:Stem Cells; D000077211:Zoledronic Acid
chemical_list: D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D007093:Imidazoles; D000077211:Zoledronic Acid
keywords: Adipose-derived stem cells; Bisphosphonate-related osteonecrosis of the jaw; Platelet-rich plasma; Zoledronic acid