Recapitulating macro-scale tissue self-organization through organoid bioprinting
Recapitulating macro-scale tissue self-organization through organoid bioprinting
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DOI：
10.1038/s41563-020-00803-5
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发表时间：
2020-09-21
期刊：
影响因子：
41.2
通讯作者：
Lutolf, Matthias P.
中科院分区：
文献类型：
--
作者：
Brassard, Jonathan A.;Nikolaev, Mike;Lutolf, Matthias P.
已经开发了一种3D生物打印方法，通过在细胞外基质中直接沉积类器官形成干细胞来促进组织形态发生，具有生成肠上皮细胞和分支血管组织构建体的能力。生物打印有望在三维（1-7）中对细胞的空间沉积进行巨大的控制，但目前的方法在复制复杂的微结构方面取得的成功有限，通过细胞自组织形成的天然组织的细胞类型多样性和功能。我们引入了一种三维生物打印概念，该概念使用类器官形成干细胞作为构建模块，可以直接沉积到有利于自发自组织的细胞外基质中。通过控制几何形状和细胞密度，我们生成了厘米级组织，其包括自组织特征，例如管腔、分支脉管系统和具有体内样隐窝和绒毛结构域的管状肠上皮。沉积支持细胞以调节空间和时间上的形态发生，并顺序打印不同的上皮细胞以模拟胃肠道中存在的器官边界。因此，我们展示了如何将生物制造技术和类器官技术合并，以控制从毫米到厘米尺度的组织自组织，为药物发现，诊断和再生医学开辟新的途径。
A 3D bioprinting approach has been developed to facilitate tissue morphogenesis by directly depositing organoid-forming stem cells in an extracellular matrix, with the ability to generate intestinal epithelia and branched vascular tissue constructs.Bioprinting promises enormous control over the spatial deposition of cells in three dimensions(1-7), but current approaches have had limited success at reproducing the intricate micro-architecture, cell-type diversity and function of native tissues formed through cellular self-organization. We introduce a three-dimensional bioprinting concept that uses organoid-forming stem cells as building blocks that can be deposited directly into extracellular matrices conducive to spontaneous self-organization. By controlling the geometry and cellular density, we generated centimetre-scale tissues that comprise self-organized features such as lumens, branched vasculature and tubular intestinal epithelia with in vivo-like crypts and villus domains. Supporting cells were deposited to modulate morphogenesis in space and time, and different epithelial cells were printed sequentially to mimic the organ boundaries present in the gastrointestinal tract. We thus show how biofabrication and organoid technology can be merged to control tissue self-organization from millimetre to centimetre scales, opening new avenues for drug discovery, diagnostics and regenerative medicine.