title: Prolonged Survival of Transplanted Osteoblastic Cells Does Not Directly Accelerate the Healing of Calvarial Bone Defects.
abstract: Considering the increased interest in cell-based bone regeneration, it is necessary to reveal the fate of transplanted cells and their substantive roles in bone regeneration. The aim of this study was to analyze the fate of transplanted cells and the effect of osteogenic cell transplantation on calvarial bone defect healing. An anti-apoptotic protein, heat shock protein (HSP) 27, was overexpressed in osteoblasts. Then, the treated osteoblasts were transplanted to calvarial bone defect and their fate was analyzed to evaluate the significance of transplanted cell survival. Transient overexpression of Hsp27 rescued MC3T3-E1 osteoblastic cells from H2 O2 -induced apoptosis without affecting osteoblastic differentiation in culture. Transplantation of Hsp27-overexpressing cells, encapsulated in collagen gel, showed higher proliferative activity, and fewer apoptotic cells in comparison with control cells. After 4-week of transplantation, both control cell- and Hsp27 overexpressed cell-transplanted groups showed significantly higher new bone formation in comparison with cell-free gel-transplantation group. Interestingly, the prolonged survival of transplanted osteoblastic cells by Hsp27 did not provide additional effect on bone healing. The transplanted cells in collagen gel survived for up to 4-week but did not differentiate into bone-forming osteoblasts. In conclusion, cell-containing collagen gel accelerated calvarial bone defect healing in comparison with cell-free collagen gel. However, prolonged survival of transplanted cells by Hsp27 overexpression did not provide additional effect. These results strongly indicate that cell transplantation-based bone regeneration cannot be explained only by the increment of osteogenic cells. Further studies are needed to elucidate the practical roles of transplanted cells that will potentiate successful bone regeneration. J. Cell. Physiol. 231: 1974-1982, 2016. © 2016 Wiley Periodicals, Inc.
authors.affiliation: Division of Bio-Prosthodontics, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.|Research Fellow of Japan Society for the Promotion of Science.
authors.forename: Megumi
authors.initials: M
authors.lastname: Kitami
authors.affiliation: Division of Bio-Prosthodontics, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.
authors.forename: Masaru
authors.initials: M
authors.lastname: Kaku
authors.affiliation: Division of Bio-Prosthodontics, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.
authors.forename: Juan Marcelo Rosales
authors.initials: JM
authors.lastname: Rocabado
authors.affiliation: Division of Bio-Prosthodontics, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.
authors.forename: Takako
authors.initials: T
authors.lastname: Ida
authors.affiliation: Division of Bio-Prosthodontics, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.
authors.forename: Nami
authors.initials: N
authors.lastname: Akiba
authors.affiliation: Division of Bio-Prosthodontics, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.
authors.forename: Katsumi
authors.initials: K
authors.lastname: Uoshima
mesh_terms: D000818:Animals; D001861:Bone Regeneration / Q000502:physiology*; D002454:Cell Differentiation / Q000502:physiology*; D002470:Cell Survival; D002478:Cells, Cultured; D003094:Collagen / Q000378:metabolism; D008297:Male; D051379:Mice; D010006:Osteoblasts / Q000166:cytology / Q000378:metabolism* / Q000637:transplantation; D010012:Osteogenesis / Q000502:physiology*; D012886:Skull / Q000601:surgery; D014945:Wound Healing / Q000502:physiology*
chemical_list: D003094:Collagen