title: On human pluripotent stem cell control: The rise of 3D bioengineering and mechanobiology.
abstract: Human pluripotent stem cells (hPSCs) provide promising resources for regenerating tissues and organs and modeling development and diseases in vitro. To fulfill their promise, the fate, function, and organization of hPSCs need to be precisely regulated in a three-dimensional (3D) environment to mimic cellular structures and functions of native tissues and organs. In the past decade, innovations in 3D culture systems with functional biomaterials have enabled efficient and versatile control of hPSC fate at the cellular level. However, we are just at the beginning of bringing hPSC-based regeneration and development and disease modeling to the tissue and organ levels. In this review, we summarize existing bioengineered culture platforms for controlling hPSC fate and function by regulating inductive mechanical and biochemical cues coexisting in the synthetic cell microenvironment. We highlight recent excitements in developing 3D hPSC-based in vitro tissue and organ models with in vivo-like cellular structures, interactions, and functions. We further discuss an emerging multifaceted mechanotransductive signaling network--with transcriptional coactivators YAP and TAZ at the center stage--that regulate fates and behaviors of mammalian cells, including hPSCs. Future development of 3D biomaterial systems should incorporate dynamically modulated mechanical and chemical properties targeting specific intracellular signaling events leading to desirable hPSC fate patterning and functional tissue formation in 3D.
authors.affiliation: Department of Mechanical Engineering, University of Michigan, Ann Arbor, MI 48109, USA.
authors.forename: Yue
authors.initials: Y
authors.lastname: Shao
authors.affiliation: Department of Mechanical Engineering, University of Michigan, Ann Arbor, MI 48109, USA.
authors.forename: Jianming
authors.initials: J
authors.lastname: Sang
authors.affiliation: Department of Mechanical Engineering, University of Michigan, Ann Arbor, MI 48109, USA; Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI 48109, USA. Electronic address: jpfu@umich.edu.
authors.forename: Jianping
authors.initials: J
authors.lastname: Fu
mesh_terms: D001672:Biocompatible Materials / Q000737:chemistry / Q000378:metabolism; D001696:Biomechanical Phenomena; D001698:Biomedical Engineering / Q000295:instrumentation / Q000379:methods; D018929:Cell Culture Techniques / Q000295:instrumentation / Q000379:methods; D002454:Cell Differentiation; D004867:Equipment Design; D006801:Humans; D039904:Pluripotent Stem Cells / Q000166:cytology* / Q000378:metabolism; D023822:Tissue Engineering / Q000295:instrumentation / Q000379:methods*
chemical_list: D001672:Biocompatible Materials
keywords: Bioengineering; Development; Human disease modeling; Human pluripotent stem cells; Mechanobiology; Regenerative medicine
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