Magnetic manipulation and spatial patterning of multi-cellular stem cell aggregates.
Magnetic manipulation and spatial patterning of multi-cellular stem cell aggregates.
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DOI：
10.1039/c1ib00064k
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发表时间：
2011-12
期刊：
影响因子：
--
通讯作者：
McDevitt TC
中科院分区：
文献类型：
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作者：
Bratt-Leal AM;Kepple KL;Carpenedo RL;Cooke MT;McDevitt TC
模仿复杂组织结构的多细胞系统的可控组装和组织对于治疗和诊断应用的组织工程至关重要。在控制多细胞聚集体形成的微尺度技术方面的最新进展通常需要对细胞和材料之间的界面进行化学修饰，并且缺乏多尺度的灵活性。在此我们证明，在初始形成过程中，将磁性微粒简单地物理包埋在干细胞球状体的细胞外空间内，能够在多个长度和时间尺度上实现无支架固定、多细胞聚集体的移位和定向组装，即使在动态悬浮培养条件下也是如此。聚集体对外加磁场的响应是微粒掺入的直接函数，从而能够对细胞外环境进行快速和瞬时控制以及对异质群体进行分离。此外，通过施加临时磁场很容易实现异质球状体群体以及单个多细胞聚集体的空间图案化。总体而言，这种方法为研究干细胞分化和组织形态发生提供了新的途径，其应用包括为发育生物学创建新的模型系统、无支架组织工程策略以及可扩展的生物加工技术。
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.