TitleMagnetic manipulation and spatial patterning of multi-cellular stem cell aggregates.
Publication TypeJournal Article
Year of Publication2011
AuthorsBratt-Leal, AM, Kepple, KL, Carpenedo, RL, Cooke, MT, McDevitt, TC
JournalIntegrative Biology
Date PublishedDecember 2011
KeywordsAnimals, Cell Aggregation, Cell Separation, Cells, Cultured, Embryonic Stem Cells, Magnetic Fields, Mice, Micromanipulation, Spheroids, Cellular

The controlled assembly and organization of multi-cellular systems to mimic complex tissue structures is critical to the engineering of tissues for therapeutic and diagnostic applications. Recent advances in micro-scale technologies to control multi-cellular aggregate formation typically require chemical modification of the interface between cells and materials and lack multi-scale flexibility. Here we demonstrate that simple physical entrapment of magnetic microparticles within the extracellular space of stem cells spheroids during initial formation enables scaffold-free immobilization, translocation and directed assembly of multi-cellular aggregates across multiple length and time scales, even under dynamic suspension culture conditions. The response of aggregates to externally applied magnetic fields was a direct function of microparticle incorporation, allowing for rapid and transient control of the extracellular environment as well as separation of heterogeneous populations. In addition, spatial patterning of heterogeneous spheroid populations as well as individual multi-cellular aggregates was readily achieved by imposing temporary magnetic fields. Overall, this approach provides novel routes to examine stem cell differentiation and tissue morphogenesis with applications that encompass the creation of new model systems for developmental biology, scaffold-free tissue engineering strategies and scalable bioprocessing technologies.

Alternate JournalIntegr Biol (Camb)
PubMed ID22076329
Grant ListT32 GM008433 / GM / NIGMS NIH HHS / United States
R01 GM088291 / GM / NIGMS NIH HHS / United States