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Issue 12, 2011
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Magnetic manipulation and spatial patterning of multi-cellular stem cell aggregates

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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.

Graphical abstract: Magnetic manipulation and spatial patterning of multi-cellular stem cell aggregates

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Supplementary files

Publication details

The article was received on 03 Jul 2011, accepted on 01 Sep 2011 and first published on 10 Nov 2011

Article type: Technical Innovation
DOI: 10.1039/C1IB00064K
Citation: Integr. Biol., 2011,3, 1224-1232

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