title: Treatment of salivary gland hypofunction by transplantation with dental pulp cells.
abstract: OBJECTIVE
  This study aimed to establish a mouse model in which dental pulp cells (DPCs) could be used as a cell source for the treatment of salivary gland hypofunction.
  
  
  METHODS
  DPCs were isolated from green fluorescent protein (GFP)-expressing mice and were differentiated into dental pulp endothelial cells (DPECs). DPEC behaviour was studied in vitro and in vivo to investigate their capacity to participate in neovascularisation. For in vivo assessment, a combination of DPECs and Matrigel was subcutaneously injected into nude mice. Two weeks after injection, Matrigel plugs were analysed for CD31 and GFP. Furthermore, both submandibular glands of the irradiated mice were injected with DPECs. Eight weeks after irradiation, the effect of DPECs on saliva secretion was evaluated by measuring amounts of saliva secretion.
  
  
  RESULTS
  DPECs showed typical endothelial morphology, including a cobblestone appearance. RT-PCR analysis of DPECs showed positive expression of CD31, foetal liver kinase-1, vascular-endothelial-cadherin, vascular endothelial growth factor-A and von Willebrand factor. DPECs reorganised into tube-like structures on Matrigel after 24h in vitro. Positive merged staining for both CD31 and GFP was observed in the tube-like structures, representative of the injected DPECs. The average saliva flow rate in mice treated with DPECs was significantly higher than that observed in mice treated with PBS (P=0.0452).
  
  
  CONCLUSIONS
  Our results show that radiation-induced salivary hypofunction is partially reverted following transplantation of DPECs. We established a mouse model in which DPCs could be used as a cell source for the treatment of salivary gland hypofunction.
authors.affiliation: Department of Oral and Maxillofacial Surgery, School of Dental Medicine, Tsurumi University, 2-1-3 Tsurumi, Tsurumi-ku, Yokohama 230-8501, Japan.
authors.forename: Yuka
authors.initials: Y
authors.lastname: Yamamura
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Yamada
authors.forename: Takashi
authors.initials: T
authors.lastname: Sakurai
authors.forename: Fumio
authors.initials: F
authors.lastname: Ide
authors.forename: Hiroko
authors.initials: H
authors.lastname: Inoue
authors.forename: Takashi
authors.initials: T
authors.lastname: Muramatsu
authors.forename: Kenji
authors.initials: K
authors.lastname: Mishima
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Hamada
authors.forename: Ichiro
authors.initials: I
authors.lastname: Saito
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000032:analysis; D015820:Cadherins / Q000032:analysis; D018929:Cell Culture Techniques; D002454:Cell Differentiation / Q000502:physiology; D002460:Cell Line; D003782:Dental Pulp / Q000166:cytology*; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000502:physiology; D004730:Endothelium, Vascular / Q000166:cytology; D005260:Female; D007279:Injections, Subcutaneous; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D008819:Mice, Nude; D055806:Microvessels / Q000254:growth & development; D018919:Neovascularization, Physiologic / Q000502:physiology; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000032:analysis; D012636:Secretory Rate / Q000502:physiology; D033581:Stem Cell Transplantation / Q000379:methods*; D013364:Submandibular Gland Diseases / Q000503:physiopathology / Q000628:therapy*; D054457:Tissue Scaffolds; D042461:Vascular Endothelial Growth Factor A / Q000032:analysis; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000032:analysis; D014987:Xerostomia / Q000503:physiopathology / Q000628:therapy*; D014841:von Willebrand Factor / Q000032:analysis; D000099152:Cadherin 5
chemical_list: D015703:Antigens, CD; D015820:Cadherins; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D042461:Vascular Endothelial Growth Factor A; D040301:Vascular Endothelial Growth Factor Receptor-2; D014841:von Willebrand Factor; D000099152:Cadherin 5; C467480:vascular endothelial growth factor A, mouse