Recapitulation of in vivo-like paracrine signals of human mesenchymal stem cells for functional neuronal differentiation of human neural stem cells in a 3D microfluidic system

Yang, Kisuk; Park, Hyun Ji; Han, Sewoon; Lee, Joon; Ko, Eunkyung; Kim, Jin; Lee, Jong Seung; Yu, Ji Hea; Song, Ki Yeong; Cheong, Eunji; Cho, Sung Rae; Chung, Seok; Cho, Seung Woo

doi:10.1016/j.biomaterials.2015.06.011

Cited by 70 publications

(61 citation statements)

References 54 publications

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“…26,30 Electrophysiological recordings of action potentials and ion channel currents from differentiated hNSCs on the GPS were carried out 5 days in the culture. To examine whether the currents and spikes were Na + channel-specific, the cells were treated with 0.5 µM tetrodotoxin (TTX) (Sigma) for 5-10 minutes.…”

Section: Electrophysiologymentioning

confidence: 99%

Graphene Oxide Hierarchical Patterns for the Derivation of Electrophysiologically Functional Neuron-like Cells from Human Neural Stem Cells

Yang

Lee

et al. 2016

ACS Appl. Mater. Interfaces

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Graphene has shown great potential for biomedical engineering applications due to its electrical conductivity, mechanical strength, flexibility, and biocompatibility. Topographical cues of culture substrates or tissue-engineering scaffolds regulate the behaviors and fate of stem cells. In this study, we developed a graphene oxide (GO)-based patterned substrate (GPS) with hierarchical structures capable of generating synergistic topographical stimulation to enhance integrin clustering, focal adhesion, and neuronal differentiation in human neural stem cells (hNSCs). The hierarchical structures of the GPS were composed of microgrooves (groove size: 5, 10, and 20 μm), ridges (height: 100-200 nm), and nanoroughness surfaces (height: ∼10 nm). hNSCs grown on the GPS exhibited highly elongated, aligned neurite extension along the ridge of the GPS and focal adhesion development that was enhanced compared to that of cells grown on GO-free flat substrates and GO substrates without the hierarchical structures. In particular, GPS with a groove width of 5 μm was found to be the most effective in activating focal adhesion signaling, such as the phosphorylation of focal adhesion kinase and paxillin, thereby improving neuronal lineage commitment. More importantly, electrophysiologically functional neuron-like cells exhibiting sodium channel currents and action potentials could be derived from hNSCs differentiated on the GPS even in the absence of any of the chemical agents typically required for neurogenesis. Our study demonstrates that GPS could be an effective culture platform for the generation of functional neuron-like cells from hNSCs, providing potent therapeutics for treating neurodegenerative diseases and neuronal disorders.

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Section: Electrophysiologymentioning

confidence: 99%

Graphene Oxide Hierarchical Patterns for the Derivation of Electrophysiologically Functional Neuron-like Cells from Human Neural Stem Cells

Yang

Lee

et al. 2016

ACS Appl. Mater. Interfaces

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“…Furthermore, PDMS can readily undergo molding, has low levels of auto-fluorescence and good transparency which facilitates cell imaging; these properties make it the first choice of bioengineers 106, 107 . In regard to neuroregeneration, numerous studies have taken advantage of these benefits to investigate the use of PDMS-based microdevices in stem cell biology, and manipulation of their fate 108–110 . However, despite these advantages, there is some difficulty in the handling and fabrication of high aspect-ratio channels, the material has low stiffness, a hydrophobic nature, and can undergo unexpected evaporation due to its porous structure, as well as possessing biocompatibility and sterilization issues, that collectively comprise its challenges 9, 92, 107 .…”

Section: Microfluidics and Tissue Engineeringmentioning

confidence: 99%

“…In this way, the pattern on the master is replicated 122 . Soft lithography-based fabrication methods have been used for production of different simple and complex microchips which have been employed in stem cell-mediated neural tissue engineering 57, 108, 115 . In this regard two additional topics should be noticed; large scale assays and integration of sensors.…”

Section: Microfluidics and Tissue Engineeringmentioning

confidence: 99%

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Microfluidic systems for stem cell-based neural tissue engineering

et al. 2016

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Neural tissue engineering aims at developing novel approaches for the treatment of diseases of the nervous system, by providing a permissive environment for the growth and differentiation of neural cells. Three-dimensional (3D) cell culture systems provide a closer biomimetic environment, and promote better cell differentiation and improved cell function, than could be achieved by conventional two-dimensional (2D) culture systems. With the recent advances in the discovery and introduction of different types of stem cells for tissue engineering, microfluidic platforms have provided an improved microenvironment for the 3D-culture of stem cells. Microfluidic systems can provide more precise control over the spatiotemporal distribution of chemical and physical cues at the cellular level compared to traditional systems. Various microsystems have been designed and fabricated for the purpose of neural tissue engineering. Enhanced neural migration and differentiation, and monitoring of these processes, as well as understanding the behavior of stem cells and their microenvironment have been obtained through application of different microfluidic-based stem cell culture and tissue engineering techniques. As the technology advances it may be possible to construct a “brain-on-a-chip”. In this review, we describe the basics of stem cells and tissue engineering as well as microfluidics-based tissue engineering approaches. We review recent testing of various microfluidic approaches for stem cell-based neural tissue engineering.

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“…MSCs also play an important role in paracrine signaling to other stem cells. For example, MSC co‐culture or MSC‐conditioned media have been found to regulate neural stem cell differentiation via the secretion of soluble signals (Bai et al, ; Yang et al, ). Overall, the types of chemicals that are applied in MSC differentiation depend on the cell lineage being targeted.…”

Section: Biochemical Stimulationmentioning

confidence: 99%

Modulation of human mesenchymal and pluripotent stem cell behavior using biophysical and biochemical cues: A review

Ding

Kingshott

Thissen

et al. 2016

Biotech & Bioengineering

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In vitro manipulation of human stem cells is a critical process in regenerative medicine and cellular therapies. Strategies and methods to maintain stem cells and direct them into specific lineages are ongoing challenges in these fields. To date, a number of studies have reported that besides biochemical stimulation, biophysical cues in the form of surface patterning and external stimulation also influence stem cell attachment, proliferation, and differentiation, and can be used in cell reprogramming and the maintenance of pluripotency. While biochemical cues are generally effective and easy to deliver, biophysical cues have many other advantages for scalability as they are cost efficient, have a longer lifetime, and can be easily defined. However, different protocols and cell sources utilized in a variety of studies have led to difficulties in obtaining clear conclusions about the effects of the biophysical environment on stem cells. In addition, the examination of different types of external stimulation is time consuming and limited by available fabrication techniques, resulting in a delay in commercialization and clinical applications. In this review, we aim to summarize the most important biophysical cues and methods for the culture of human stem cells, including mesenchymal and pluripotent stem cells, to facilitate their adoption in stem cell biology. The standard classical protocols of using biochemical cues will also be discussed for comparison. We believe that combining biochemical and biophysical stimulation has the greatest potential to generate functionally mature cells at a scalable and inexpensive rate for diverse applications in regenerative medicine and cell therapy. Biotechnol. Bioeng. 2017;114: 260-280. © 2016 Wiley Periodicals, Inc.

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Recapitulation of in vivo-like paracrine signals of human mesenchymal stem cells for functional neuronal differentiation of human neural stem cells in a 3D microfluidic system

Cited by 70 publications

References 54 publications

Graphene Oxide Hierarchical Patterns for the Derivation of Electrophysiologically Functional Neuron-like Cells from Human Neural Stem Cells

Graphene Oxide Hierarchical Patterns for the Derivation of Electrophysiologically Functional Neuron-like Cells from Human Neural Stem Cells

Microfluidic systems for stem cell-based neural tissue engineering

Modulation of human mesenchymal and pluripotent stem cell behavior using biophysical and biochemical cues: A review

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