title: Bone regeneration in calvarial defects in a rat model by implantation of human bone marrow-derived mesenchymal stromal cell spheroids.
abstract: Mesenchymal stem cell (MSC) condensation contributes to membrane ossification by enhancing their osteodifferentiation. We investigated bone regeneration in rats using the human bone marrow-derived MSC-spheroids prepared by rotation culture, without synthetic or exogenous biomaterials. Bilateral calvarial defects (8 mm) were created in nude male rats; the left-sided defects were implanted with MSC-spheroids, β-tricalcium phosphate (β-TCP) granules, or β-TCP granules + MSC-spheroids, while the right-sided defects served as internal controls. Micro-computed tomography and immunohistochemical staining for osteocalcin/osteopontin indicated formation of new, full-thickness bones at the implantation sites, but not at the control sites in the MSC-spheroid group. Raman spectroscopy revealed similarity in the spectral properties of the repaired bone and native calvarial bone. Mechanical performance of the bones in the MSC-implanted group was good (50 and 60% those of native bones, respectively). All tests showed poor bone regeneration in the β-TCP and β-TCP + MSC-spheroid groups. Thus, significant bone regeneration was achieved with MSC-spheroid implantation into bone defects, justifying further investigation.
authors.affiliation: Department of Oral-Maxillofacial Surgery, Dentistry and Orthodontics, The University of Tokyo Hospital, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan. suenaga-tky@umin.ac.jp.
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Suenaga
authors.affiliation: Biomedical Engineering Laboratory, Department of Bioengineering and Mechanical Engineering, Graduate School of Engineering, The University of Tokyo, Tokyo, Japan.
authors.forename: Katsuko S
authors.initials: KS
authors.lastname: Furukawa
authors.affiliation: Department of Oral-Maxillofacial Surgery, Dentistry and Orthodontics, The University of Tokyo Hospital, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan.
authors.forename: Yukako
authors.initials: Y
authors.lastname: Suzuki
authors.affiliation: Department of Oral-Maxillofacial Surgery, Dentistry and Orthodontics, The University of Tokyo Hospital, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan.|Division of Tissue Engineering, The University of Tokyo Hospital, Tokyo, Japan.
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Takato
authors.affiliation: Center for Disease Biology and Integrative Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Ushida
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology*; D001861:Bone Regeneration; D017690:Cell Transplantation; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D051379:Mice; D008819:Mice, Nude; D023421:Models, Animal; D051381:Rats; D012886:Skull / Q000002:abnormalities*; D013059:Spectrum Analysis, Raman; D018874:Spheroids, Cellular; D055114:X-Ray Microtomography