Microfluidic device to control interstitial flow-mediated homotypic and heterotypic cellular communication.
Microfluidic device to control interstitial flow-mediated homotypic and heterotypic cellular communication.
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DOI：
10.1039/c5lc00507h
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发表时间：
2015-09-07
期刊：
影响因子：
6.1
通讯作者：
George SC
中科院分区：
文献类型：
--
作者：
Alonzo LF;Moya ML;Shirure VS;George SC
组织工程可以在体外重建体内细胞微环境，用于生物学研究和药物发现等一系列应用。然而，目前大多数体外系统仍然忽视了许多已知影响细胞功能如增殖、迁移和分化的生物、化学和机械因素。为了解决这一差距，我们开发了一种新型的微流体装置，可以精确控制相邻三维细胞环境之间的空间和时间相互作用。该装置由四个相互连接的微组织隔室（~0.1 mm 3）组成，排列成正方形。顶部和底部成对的隔室可以顺序地装载有分离的细胞化水凝胶，从而创造了研究同型（从左到右或x方向）和异型（从上到下或y方向）细胞-细胞通信的机会。在x和y方向上跨组织隔室的受控流体静压差诱导间质流并通过可溶性因子调节通信。为了验证这个新平台的生物学意义，我们研究了基质细胞在血管发生过程中的作用。我们的装置证实了以前的观察结果，即来源于正常人肺成纤维细胞（NHLF）的可溶性介质是形成来源于内皮集落形成细胞衍生的内皮细胞（ECFC-EC）的血管网络所必需的。我们的结论是，该平台可用于研究依赖于同型和异型细胞间通讯的重要生理和病理过程。
Tissue engineering can potentially recreate in vivo cellular microenvironments in vitro for an array of applications such as biological inquiry and drug discovery. However, the majority of current in vitro systems still neglect many biological, chemical, and mechanical cues that are known to impact cellular fucntions such as proliferation, migration, and differentiation. To address this gap, we have developed a novel microfluidic device that precisely controls the spatial and temporal interactions between adjacent three-dimensional cellular environments. The device consists of four interconnected microtissue compartments (~0.1 mm3) arranged in a square. The top and bottom pairs of compartments can be sequentially loaded with discreate cellularized hydrogels creating the opportunity to investigate homotypic (left to right or x-direction) and heterotypic (top to bottom or y-direction) cell-cell communication. A controlled hydrostatic pressure difference across the tissue compartments in both x and y direction induces interstitial flow and modulates communication via soluble factors. To validate the biological significance of this novel platform, we examined the role of stromal cells in the process of vasculogenesis. Our device confirms previous observations that soluble mediators derived from normal human lung fibroblasts (NHLFs) are necessary to form a vascular network derived from endothelial colony forming cell-derived endothelial cells (ECFC-ECs). We conclude that this platfrom could be used to study important physiological and pathological processes that rely on homotypic and heterotypic cell-cell communication.