Bone regeneration in calvarial defects in a rat model by implantation of human bone marrow-derived mesenchymal stromal cell spheroids

• DOI: 10.1007/s10856-015-5591-3
• Publication Date: 2015-10-08T12:26:52Z
• Authors: Hideyuki Suenaga; Katsuko S. Furukawa; Yukako Suzuki; Tsuyoshi Takato; Takashi Ushida
• Keywords: 0301 basic medicine; Bone Regeneration; Cell Transplantation; Tissue Engineering Constructs and Cell Substrates; Skull; Biophysics; Mice, Nude; Bioengineering; Bone Marrow Cells; Mesenchymal Stem Cells; X-Ray Microtomography; Spectrum Analysis, Raman; Rats; Mice; 03 medical and health sciences; Spheroids, Cellular; Models, Animal; Chemical Engineering(all); Animals; Humans

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.