Three-dimensional bioprinted cancer models: A powerful platform for investigating tunneling nanotube-like cell structures in complex microenvironments
Three-dimensional bioprinted cancer models: A powerful platform for investigating tunneling nanotube-like cell structures in complex microenvironments
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DOI：
10.1016/j.msec.2021.112357
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发表时间：
2021-08-12
影响因子：
7.9
通讯作者：
Chiara, Maria-Dolores
中科院分区：
文献类型：
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作者：
Herrada-Manchon, Helena;Celada, Lucia;Chiara, Maria-Dolores
生物打印技术提供了细胞在三维空间中的逐层定位，具有复杂性和明确的结构。基于这种生物制造技术的肿瘤模型是实现具有代表性和真实的肿瘤微环境在体内条件的重要工具。在这里，我们展示了一个概念验证的三维生物打印癌症模型的发展，该模型通过功能隧道纳米管（TNT）样细胞投影的组装成功地概括了细胞间的通信。初步制备了含胶原培养基、海藻酸钠和明胶的不同组合，并对其进行了流变学评价。利用优化后的混合物打印了两个用于癌细胞播种的初步3D模型。细胞活力和增殖的良好结果导致将786-O肾癌细胞包含在生物材料混合物中，直接生物打印最合适的3D模型。生物打印的细胞在至少15天的培养和增殖中保持活力。更重要的是，这些癌细胞能够在水凝胶内建立类似tnt的细胞突起，从而在远处的细胞之间建立直接联系。我们表明，这些结构被用作线粒体滚动和细胞间转移的通道，从而在二维培养系统中再现了TNT的功能。这种生物3D打印的肾癌模型为在高度可控和可复制的肿瘤微环境中研究tnt样结构在肿瘤发生和抗癌药物敏感性中的功能相关性提供了一种新的替代工具。
Bioprinting technology offers layer-by-layer positioning of cells within 3D space with complexity and a defined architecture. Cancer models based in this biofabrication technique are important tools to achieve representative and realistic in vivo conditions of the tumor microenvironment. Here, we show the development of a proof-ofconcept three-dimensional bioprinted cancer model that successfully recapitulates the intercellular communication via the assembly of functional tunneling nanotube (TNT)-like cell projections. Different combinations of collagen-containing culture medium, sodium alginate and gelatin were initially prepared and rheologically evaluated. The optimized mixture was used to print two preliminary 3D models for cancer cell seeding. Favourable results in cell viability and proliferation led to the inclusion of 786-O renal cancer cells into the biomaterial mixture to directly bioprint the most suitable 3D model with embedded cells. Bioprinted cells remained viable for at least 15 days of culture and proliferated. More importantly, these cancer cells were able to build TNT-like cellular projections inside the hydrogel that established direct contacts between distant cells. We show that these structures were used as channels for the scrolling and intercellular transfer of mitochondria thus reproducing TNT's function in 2D culture systems. This 3D bioprinted renal cancer model provides a novel alternative tool for studying the functional relevance of TNT-like structures in tumorigenesis and anticancer drug susceptibility in a highly controlled and reproducible tumor microenvironment.