Microfluidic Organs-on-Chips to Reconstitute Cellular Microenvironments
Recent advances in microsystems technology and tissue engineering have led to the development of biomimetic microdevices to model key functional units of human organs, known as organs-on-chips. By mimicking natural tissue architecture and microenvironment
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Microfluidic Organs-on-Chips to Reconstitute Cellular Microenvironments Yu-suke Torisawa
Abstract Recent advances in microsystems technology and tissue engineering have led to the development of biomimetic microdevices to model key functional units of human organs, known as organs-on-chips. By mimicking natural tissue architecture and microenvironmental chemical and physical cues within microfluidic devices, this technology realizes organ-level function in vitro that cannot be recapitulated with conventional culture methods. Since the physiological microenvironments in living systems are mostly microfluidic in nature, microfluidic systems facilitate engineering of cellular microenvironments. Microfluidic systems allow for control of local chemical gradients and dynamic mechanical forces, which play important roles in organ development and function. This organ-on-a-chip technology has great potential to facilitate drug discovery and development, to model human physiology and disease, and to replace animal models for efficacy and toxicity testing. This chapter shows an overview of the organ-on-a-chip technology to recapitulate cellular microenvironments and especially focuses on bone marrow-on-a-chip that enables culture of living bone marrow with a functional hematopoietic niche as a novel type of approach to develop organs-on-chips. Keywords Organs-on-chips · Microfluidics · Tissue engineering · Cellular microenvironment
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Introduction Cellular Microenvironment
Cellular functions are precisely controlled by their specific microenvironment where they normally reside. The microenvironment contains a complex set of structural, Y.-s. Torisawa (*) Hakubi Center for Advanced Research and Department of Micro Engineering, Kyoto University, Kyoto, Japan e-mail: [email protected] © Springer Nature Singapore Pte Ltd. 2019 M. Tokeshi (ed.), Applications of Microfluidic Systems in Biology and Medicine, Bioanalysis 7, https://doi.org/10.1007/978-981-13-6229-3_8
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chemical, and mechanical signals which are necessary to maintain cellular viability and function [1–3]. Since stem cells cannot maintain their stemness without specific stem cell niches [3–5], cellular microenvironments are crucial for maintaining cellular function, whereas current conventional culture methods do not contain these microenvironmental cues correctly. Because of this microenvironmental gap, cellular functions and responses in vitro are very different from those in vivo, and thus conventional 2D cultures cannot accurately predict cellular functions and responses inside the body [6–8]. It is necessary to reconstitute cellular microenvironments for developing reliable in vitro methods. Development of biomimetic microdevices that can recapitulate tissue structure and microenvironmental cues could be a useful platform to facilitate drug discovery and development and to develop predictive models of human physiology and diseases.
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Cellular Microenvironments Within Microfluidic Systems
The physiological microenviro
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