Abstract
Abstract Regenerative medicine requires new ways to assemble and manipulate cells for fabrication of tissue-like constructs. Here we report a novel approach for cell surface engineering of human cells using polymer-stabilized magnetic nanoparticles (MNPs). Cationic polyelectrolyte-coated MNPs are directly deposited onto cellular membranes, producing a mesoporous semi-permeable layer and rendering cells magnetically responsive. Deposition of MNPs can be completed within minutes, under cell-friendly conditions (room temperature and physiologic media). Microscopy (TEM, SEM, AFM, and enhanced dark-field imaging) revealed the intercalation of nanoparticles into the cellular microvilli network. A detailed viability investigation was performed and suggested that MNPs do not inhibit membrane integrity, enzymatic activity, adhesion, proliferation, or cytoskeleton formation, and do not induce apoptosis in either cancer or primary cells. Finally, magnetically functionalized cells were employed to fabricate viable layered planar (two-cell layers) cell sheets and 3D multicellular spheroids.
Highlights
Driven assembly of human cells into artificial multicellular clusters mimicking human tissues is regarded as a powerful tool in regenerative medicine [1, 2].Magnetically facilitated tissue engineering employs the introduction of magnetic nanoparticles (MNPs)Nano Res. 2015, 8(8): 2515–2532 implementation of MNPs-modified cells in fabrication of artificial constructs imitating vascular tissue [4], skeletal muscle tissues [5], and keratinocyte sheets [6]
To minimize the potential toxic effects of MNPs, several recent studies have suggested using MNPs isolated from magnetotactic bacteria [17], which are believed to be less toxic than chemically synthesized MNPs, fabrication of magnetoferritin nanoparticles, or construction of Janus magnetic cellular spheroids by concentrating nanoparticles in certain regions of spheroids, reducing MNPs–cell interactions [8]
We report the detailed study of cell surface engineering of human cells with polyelectrolytestabilized MNPs and demonstrate the magnetically facilitated fabrication of artificial multicellular clusters using MNPs-functionalized cells
Summary
Driven assembly of human cells into artificial multicellular clusters mimicking human tissues is regarded as a powerful tool in regenerative medicine [1, 2]. To minimize the potential toxic effects of MNPs, several recent studies have suggested using MNPs isolated from magnetotactic bacteria [17], which are believed to be less toxic than chemically synthesized MNPs, fabrication of magnetoferritin nanoparticles, or construction of Janus magnetic cellular spheroids by concentrating nanoparticles in certain regions of spheroids, reducing MNPs–cell interactions [8]. Effective, these approaches are rather complex and require time-consuming manipulation of cells or sophisticated methods of nanoparticle preparation. Cell surface engineering with PAH-MNPs allowed us to fabricate layered tissue-like clusters and multicellular spheroids, demonstrating the potential of our approach for tissue engineering
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