Scaffold-free formation of a millimeter-scale multicellular spheroid with an internal cavity from magnetically levitated 3T3 cells that ingested iron oxide-containing microspheres


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This report describes fabrication of a millimeter-scale three-dimensional (3D) multicellular structure with a central cavity based on magnetic levitation of 3T3 cells that had ingested Fe3O4-containing microcapsules. Magnetically levitated cells initially formed a disc-shaped cell cluster at the air-medium interface and transformed into a spheroid (up to 2.8 mm in diameter) after 10-day incubation under a magnet. Hematoxylin-and-eosin-stained section revealed that an eosinophilic shell of cells enclosed a pale-staining core of the spheroid. Mitotic or elongated and aligned cells were found at the outer periphery of the shell, while Fe3O4 deposits were distributed in the inner part of the shell. Surgical dissection indicated that the spheroid had a hollow interior filled with a fluid-state cell suspension. Accordingly, it was demonstrated that magnetically levitated 3T3 cells organized themselves into a tissue-like spheroid, resulting in core cell death. The spheroid can be used as a 3D tissue model and as building blocks that fused to form a more complicated structure. Biotechnol. Biotechnol. Bioeng. 2014;111: 1038–1047. © 2013 Wiley Periodicals, Inc.