Engineered Micromechanical Cues Affecting Human Pluripotent Stem Cell Regulations and Fate

Nampe, Daniel; Tsutsui, Hideaki

doi:10.1177/2211068213503156

Cited by 13 publications

(12 citation statements)

References 126 publications

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“…The physical and chemical properties of cellular microenvironments (e.g., matrix stiffness, gradient of chemokines and growth factors) are known to significantly influence and direct the differentiation process of stem cells [26,[30][31][32][33]. Microfluidic systems also enable minimization of the sample size, allowing costly reagents to be used in smaller quantities, and provide a dynamic platform for high-throughput screening of chemicals or drugs [34,35].…”

Section: Designing a Microfluidic Device For Sustainable Long-term Dymentioning

confidence: 99%

Functional Maintenance of Differentiated Embryoid Bodies in Microfluidic Systems: A Platform for Personalized Medicine

Güven

Lindsey

Poudel

et al. 2015

Stem Cells Translational Medicine

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Hormone replacement therapies have become important for treating diseases such as premature ovarian failure or menopausal complications. The clinical use of bioidentical hormones might significantly reduce some of the potential risks reportedly associated with the use of synthetic hormones. In the present study, we demonstrate the utility and advantage of a microfluidic chip culture system to enhance the development of personalized, on-demand, treatment modules using embryoid bodies (EBs). Functional EBs cultured on microfluidic chips represent a platform for personalized, patient-specific treatment cassettes that can be cryopreserved until required for treatment. We assessed the viability, differentiation, and functionality of EBs cultured and cryopreserved in this system. During extended microfluidic culture, estradiol, progesterone, testosterone, and anti-müllerian hormone levels were measured, and the expression of differentiated steroidogenic cells was confirmed by immunocytochemistry assay for the ovarian tissue markers anti-müllerian hormone receptor type II, follicle-stimulating hormone receptor, and inhibin b-A and the estrogen biosynthesis enzyme aromatase. Our studies showed that under microfluidic conditions, differentiated steroidogenic EBs continued to secrete estradiol and progesterone at physiologically relevant concentrations (30-120 pg/ml and 150-450 pg/ml, respectively) for up to 21 days. Collectively, we have demonstrated for the first time the feasibility of using a microfluidic chip system with continuous flow for the differentiation and extended culture of functional steroidogenic stem cell-derived EBs, the differentiation of EBs into cells expressing ovarian antigens in a microfluidic system, and the ability to cryopreserve this system with restoration of growth and functionality on thawing. These results present a platform for the development of a new therapeutic system for personalized medicine. STEM CELLS TRANSLATIONAL MEDICINE 2015;4:261-268

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Section: Designing a Microfluidic Device For Sustainable Long-term Dymentioning

confidence: 99%

Functional Maintenance of Differentiated Embryoid Bodies in Microfluidic Systems: A Platform for Personalized Medicine

Güven

Lindsey

Poudel

et al. 2015

Stem Cells Translational Medicine

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“…Binding of the cell to the substrate is the first stage to transmitting force across the cell membrane, 3,9,18,20 and through this binding, integrins interact with the extracellular environment. 21 Next, adaptor proteins bind to actin in the cytoskeleton, linking it to the cell membrane. Then, forces are transmitted from the actin filaments through the myosin head.…”

Section: Mechanotransduction Pathwaysmentioning

confidence: 99%

Mechanotransduction of Neural Cells Through Cell–Substrate Interactions

Stukel

Willits

2016

Tissue Engineering Part B: Reviews

102

100

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Neurons and neural stem cells are sensitive to their mechanical and topographical environment, and cell-substrate binding contributes to this sensitivity to activate signaling pathways for basic cell functions. Many transmembrane proteins transmit signals into and out of the cell, including integrins, growth factor receptors, G-protein-coupled receptors, cadherins, cell adhesion molecules, and ion channels. Specifically, integrins are one of the main transmembrane proteins that transmit force across the cell membrane between a cell and its extracellular matrix, making them critical in the study of cell-material interactions. This review focuses on mechanotransduction, defined as the conversion of force a cell generates through cell-substrate bonds to a chemical signal, of neural cells. The chemical signals relay information via pathways through the cellular cytoplasm to the nucleus, where signaling events can affect gene expression. Pathways and the cellular response initiated by substrate binding are explored to better understand their effect on neural cells mechanotransduction. As the results of mechanotransduction affect cell adhesion, cell shape, and differentiation, knowledge regarding neural mechanotransduction is critical for most regenerative strategies in tissue engineering, where novel environments are developed to improve conduit design for central and peripheral nervous system repair in vivo.

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“…In fact, preliminary attempts to replicate the experiments by Bosco et al (1997b) resulted in extensive cell death/loss where only a small central vesicular structure remained, which raised concerns about the integrity of those free floating cultures (data not shown). Given past insights into tissue and cell morphology affecting cell proliferation (Watt et al, 1988), survival (Folkman & Greenspan, 1975;Chen et al, 1997), signaling (Rangamani et al, 2013), and differentiation (Kumar et al, 2011;Nampe & Tsutsui, 2013), it is likely that morphology may also play a key role in Xenopus lens regeneration.…”

Section: The Potential Effects Of Morphology In Cornea Culturesmentioning

confidence: 99%

FGF1 PromotesXenopus laevisLens Regeneration

Moore

Sun

et al. 2018

Preprint

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Background:The frog Xenopus laevis has notable regenerative capabilities, including that of the lens. The neural retina provides the factors that trigger lens regeneration from the cornea, but the identity of these factors is largely unknown. In contrast to the cornea, fibroblast growth factors FGF1, 8, and 9 are highly expressed within the retina, and are potential candidates for those factors. The purpose of this study is to determine whether specific FGF proteins can induce lens formation, and if perturbation of FGFR signaling inhibits lens regeneration. Methods:A novel cornea epithelial culture method was developed to investigate the sufficiency of FGFs in lens regeneration. Additionally, transgenic larvae expressing dominant negative FGFR1 were used to investigate the necessity of FGFR signaling in lens regeneration.Results: Treatment of cultured corneas with FGF1 induced lens regeneration in a dosedependent manner, whereas treatment with FGF2, FGF8, or FGF9 did not result in significant lens regeneration. Inhibition of FGFR signaling decreased the lens regeneration rate for in vitro eye cultures. Conclusion:The culture techniques developed here, and elsewhere, have provided reliable methods for examining the necessity of various factors that may be involved in lens regeneration.Based on the results demonstrated in this study, we found that FGF1 signaling and FGFR activation are key factors for lens regeneration in Xenopus.

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Engineered Micromechanical Cues Affecting Human Pluripotent Stem Cell Regulations and Fate

Cited by 13 publications

References 126 publications

Functional Maintenance of Differentiated Embryoid Bodies in Microfluidic Systems: A Platform for Personalized Medicine

Functional Maintenance of Differentiated Embryoid Bodies in Microfluidic Systems: A Platform for Personalized Medicine

Mechanotransduction of Neural Cells Through Cell–Substrate Interactions

FGF1 PromotesXenopus laevisLens Regeneration

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