Hydrogel-integrated Microfluidic Systems for Advanced Stem Cell Engineering
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Review Article
Hydrogel-integrated Microfluidic Systems for Advanced Stem Cell Engineering Soohwan An, Seung Yeop Han & Seung-Woo Cho
*
Received: 9 November, 2019 / Accepted: 10 December, 2019 / Published online: 18 December, 2019 â’¸The Korean BioChip Society and Springer 2019
Abstract Previous culture techniques are often ineffective for providing appropriate conditions to cells grown in vitro for efficient growth and maturation. However, the advent of microfluidic chips allows us to manipulate various factors from co-culturing cells to inducing shear stress and biochemical gradient. The above have all been effectively applied to stem cell engineering, allowing dynamic interactions with other cells and, as a result, acquisition of a more mature state. The introduction of both synthetic and natural hydrogels into the chip provides more precise in vivo-like biophysical and biochemical cues to cells, enabling better recapitulation of the in vivo-like physiological behaviors and further maturation of stem cells even to the scale of organoids. This review addresses fundamental roles of microfluidic chips and hydrogels and how hydrogel-integrated chip systems provide breakthroughs in advanced stem cell engineering. Keywords: Hydrogel, Microenvironment, Microfluidics, Organoid, Stem cell
Introduction Decades of study in stem cell biology have significantly advanced our understanding and ability to culture various types of stem cells and control their behaviors in vitro. Although the recent advances have improved exploitation of various stem cell sources Department of Biotechnology, Yonsei University, Seoul 03722, Republic of Korea *Correspondence and requests for materials should be addressed to S.-W. Cho ( [email protected])
for regenerative medicine and better modeling of various tissues for precision medicine and drug screening, several important limitations have not been met yet, such as low differentiation efficiency, insufficient functional maturity, and weak correlation with physiology in vivo1,2. Recently, the importance of the cellular microenvironment, including various biological, chemical, and even physical cues, for precise control of cellular behaviors has been emphasized3-7. The microenvironment surrounding stem cells, called stem cell niche, can greatly influence their behaviors8-11. However, the conventional stem cell culture techniques often cannot provide proper microenvironments, which is one of the factors contributing to the limitations mentioned above. Microfluidic chips, which deal with fluids that are geometrically constrained to a small volume, have been considered as one of the best candidates for reconstituting cellular microenvironments since they facilitate precise control and manipulation of microscale behaviors of the fluid to exquisitely regulate several factors within the microenvironment12-14. Many previous studies have shown the potential and benefits of using microfluidics for culture and control of stem cell behaviors through proper regulation of the microenvironment15-17
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