Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, San Francisco, California, 94158, United States of America.
Department of Medicine, University of California, San Francisco, San Francisco, California, 94158, United States of America.
Biofabrication. 2022 Aug 23;14(4). doi: 10.1088/1758-5090/ac8622.
Multicellular liver spheroids are 3D culture models useful in the development of therapies for liver fibrosis. While these models can recapitulate fibrotic disease, current methods for generating them via random aggregation are uncontrolled, yielding spheroids of variable size, function, and utility. Here, we report fabrication of precision liver spheroids with microfluidic flow cytometric printing. Our approach fabricates spheroids cell-by-cell, yielding structures with exact numbers of different cell types. Because spheroid function depends on composition, our precision spheroids have superior functional uniformity, allowing more accurate and statistically significant screens compared to randomly generated spheroids. The approach produces thousands of spheroids per hour, and thus affords a scalable platform by which to manufacture single-cell precision spheroids for disease modeling and high throughput drug testing.
多细胞肝球体是 3D 培养模型，可用于开发肝纤维化治疗方法。虽然这些模型可以重现纤维化疾病，但目前通过随机聚集生成它们的方法是不可控的，会产生大小、功能和用途各不相同的球体。在这里，我们报告了使用微流控流式细胞术打印制造精密肝球体的方法。我们的方法逐个细胞地制造球体，产生具有确切数量的不同细胞类型的结构。由于球体的功能取决于组成，因此我们的精密球体具有更好的功能均匀性，与随机生成的球体相比，可以进行更准确和更具统计学意义的筛选。该方法每小时可生产数千个球体，因此提供了一个可扩展的平台，可以制造用于疾病建模和高通量药物测试的单细胞精密球体。
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