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Embryonic stem cell bioprinting for uniform and controlled size embryoid body formation
Authors:Xu Feng  Sridharan Banupriya  Wang Shuqi  Gurkan Umut Atakan  Syverud Brian  Demirci Utkan
Institution:1.Department of Medicine, Demirci Bio-Acoustic-MEMS in Medicine (BAMM) Laboratory, Center for Biomedical Engineering, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts 02139, USA;2.Digilab Inc., 84 October Hill Road, Holliston, Massachusetts 01746, USA;3.Harvard-MIT Health Sciences and Technology, Cambridge, Massachusetts 02139, USA
Abstract:Embryonic stem cells (ESCs) are pluripotent with multilineage potential to differentiate into virtually all cell types in the organism and thus hold a great promise for cell therapy and regenerative medicine. In vitro differentiation of ESCs starts with a phase known as embryoid body (EB) formation. EB mimics the early stages of embryogenesis and plays an essential role in ESC differentiation in vitro. EB uniformity and size are critical parameters that directly influence the phenotype expression of ESCs. Various methods have been developed to form EBs, which involve natural aggregation of cells. However, challenges persist to form EBs with controlled size, shape, and uniformity in a reproducible manner. The current hanging-drop methods are labor intensive and time consuming. In this study, we report an approach to form controllable, uniform-sized EBs by integrating bioprinting technologies with the existing hanging-drop method. The approach presented here is simple, robust, and rapid. We present significantly enhanced EB size uniformity compared to the conventional manual hanging-drop method.
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