The promotion of neuronal maturation on soft substrates

Teixeira, Ana I.; Ilkhanizadeh, Shirin; Wigenius, Jens; Duckworth, Joshua K.; Inganäs, Olle; Hermanson, Ola

doi:10.1016/j.biomaterials.2009.05.013

Cited by 172 publications

(159 citation statements)

References 22 publications

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“…Reduced glial growth in PEG hydrogels may be attributable to reduced substrate stiffness given that decreased GFAP expression was also observed in 2D-PEG cultures, and that previous reports have shown decreasing GFAP expression and neural cell proliferation on substrates of decreasing stiffnes. 26 While a recent study reported decreases in GFAP expression on poly(dimethylsiloxane) substrates of increasing stiffness, 11 the results observed here are substantiated by a mechanistic study demonstrating reduced actin polymerization within glia and suppressed glial proliferation upon soft substrates. 12 Additional studies are needed to determine the mechanism by which neural cells sense substrate stiffness, possibly through traditional mechanotransduction after cell-secreted ECM proteins adsorb to the polymer surface.…”

Section: Dapt Supplementationsupporting

confidence: 73%

“…8,9 Still other soluble factors such as the g-secretase inhibitor, N-[N-(3,5-difluorophenacetyl)-l-alanyl]-S-phenylglycine t-butyl ester (DAPT), can increase the percentage of NPCs that undergo neuronal rather than glial differentiation. 10,11 Much of this research has been performed in monolayer culture; however, characterizing and controlling NPCs within three-dimensional (3D) tissue engineering matrices is of increasing importance given the potential of these matrices to support integration of transplanted cells. [12][13][14][15][16] Poly(ethylene glycol) (PEG)-based hydrogels are a particularly useful matrix for studying the effects of soluble factors on NPC behavior in 3D because, like monolayer cultures, they provide a minimally instructive environment devoid of exogenous peptides.…”

Section: Introductionmentioning

confidence: 99%

“…DAPT supplementation may be an effective approach given that, even in cell dense cultures, DAPT can inhibit the ligand-dependent, g-secretase-mediated cleavage and activation of notch receptors that is required for the onset of gliogenesis. 10,11,37,38 Materials and Methods…”

Section: Introductionmentioning

confidence: 99%

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Control of Neural Cell Composition in Poly(Ethylene Glycol) Hydrogel Culture with Soluble Factors

Mooney

Haeger

Lawal

et al. 2011

Tissue Engineering Part A

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Poly(ethylene glycol) (PEG) hydrogels are being developed as cell delivery vehicles that have great potential to improve neuronal replacement therapies. Current research priorities include (1) characterizing neural cell growth within PEG hydrogels relative to standard culture systems and (2) generating neuronal-enriched populations within the PEG hydrogel environment. This study compares the percentage of neural precursor cells (NPCs), neurons, and glia present when dissociated neural cells are seeded within PEG hydrogels relative to standard monolayer culture. Results demonstrate that PEG hydrogels enriched the initial cell population for NPCs, which subsequently gave rise to neurons, then to glia. Relative to monolayer culture, PEG hydrogels maintained an increased percentage of NPCs and a decreased percentage of glia. This neurogenic advantage of PEG hydrogels is accentuated in the presence of basic fibroblast growth factor and epidermal growth factor, which more potently increase NPC and neuronal expression markers when applied to cells cultured within PEG hydrogels. Finally, this work demonstrates that glial differentiation can be selectively eliminated upon supplementation with a g-secretase inhibitor. Together, this study furthers our understanding of how the PEG hydrogel environment influences neural cell composition and also describes select soluble factors that are useful in generating neuronal-enriched populations within the PEG hydrogel environment.

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Section: Dapt Supplementationsupporting

confidence: 73%

Section: Introductionmentioning

confidence: 99%

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Control of Neural Cell Composition in Poly(Ethylene Glycol) Hydrogel Culture with Soluble Factors

Mooney

Haeger

Lawal

et al. 2011

Tissue Engineering Part A

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“…However, developmental processes such as axon pathfinding, synapse formation, nervous system patterning, neuronal plasticity, and degeneration fail to be explained solely on the basis of soluble factors. There is increasing evidence that physical variables such as the stiffness of a cellular environment influence cell development (7)(8)(9)(10)(11)(12). However, the cells of the brain tissue reside in a soft environment that is rich in polysaccharides (13,14).…”

mentioning

confidence: 99%

Stochastic nanoroughness modulates neuron–astrocyte interactions and function via mechanosensing cation channels

Blumenthal¹,

Hermanson

Heimrich

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

139

135

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Extracellular soluble signals are known to play a critical role in maintaining neuronal function and homeostasis in the CNS. However, the CNS is also composed of extracellular matrix macromolecules and glia support cells, and the contribution of the physical attributes of these components in maintenance and regulation of neuronal function is not well understood. Because these components possess well-defined topography, we theorize a role for topography in neuronal development and we demonstrate that survival and function of hippocampal neurons and differentiation of telencephalic neural stem cells is modulated by nanoroughness. At roughnesses corresponding to that of healthy astrocytes, hippocampal neurons dissociated and survived independent from astrocytes and showed superior functional traits (increased polarity and calcium flux). Furthermore, telencephalic neural stem cells differentiated into neurons even under exogenous signals that favor astrocytic differentiation. The decoupling of neurons from astrocytes seemed to be triggered by changes to astrocyte apical-surface topography in response to nanoroughness. Blocking signaling through mechanosensing cation channels using GsMTx4 negated the ability of neurons to sense the nanoroughness and promoted decoupling of neurons from astrocytes, thus providing direct evidence for the role of nanotopography in neuron-astrocyte interactions. We extrapolate the role of topography to neurodegenerative conditions and show that regions of amyloid plaque buildup in brain tissue of Alzheimer's patients are accompanied by detrimental changes in tissue roughness. These findings suggest a role for astrocyte and ECM-induced topographical changes in neuronal pathologies and provide new insights for developing therapeutic targets and engineering of neural biomaterials. mechanotransduction | stretch-activated channels | FAM38A | Piezo-1 | polarization

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“…Outros ensaios envolvendo os polímeros PCL, PLGA e o copolímero poli L -co-D , L -ácido láctico (PLDLA), conferiram o caráter de serem biocompatíveis e mantiveram a viabilidade celular in vitro [11][12][13]15,21] . Já, quando aplicados os biomateriais no sistema nervoso central, estes se mostraram viáveis e provocaram a diferenciação celular e maturação neuronal [22,23] . Segundo Teixeira et al [22] , quando o substrato apresenta as mesmas características do tecido cerebral, ou seja, a propriedade mecânica da elasticidade, este tem a capacidade de promover a maturação e a diferenciação de células indiferenciadas em neurônios e também realizar a sustentação e proliferação dos astrócitos.…”

Section: Introductionunclassified

Estudo das células Neuro2A sobre os biomateriais PCL e PLLA

et al. 2014

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Resumo: Os biomateriais poli L-ácido lático (PLLA) e o poli caprolactona (PCL) são os polímeros mais estudadas na área dos materiais bioreabsorvíveis. Dentre as suas principais características que contribuem para a interação celular, temos a especificidade química da superfície, elétrica, hidrofobicidade e topografia. Ainda, observa-se o tempo de degradação, porosidade, biocompatibilidade com o tecido biológico, bem como, a confecção com as mais variadas formas e dimensões. Já a prática da cultura celular, tem como objetivo estudar a adesão, migração, diferenciação e a proliferação celular utilizando-se um determinado material ou substância. Contudo, poucos trabalhos utilizando os biomateriais ora supracitados e a aplicação em células neuro2A foram realizados. Sabe-se que este tipo celular é derivado de células embrionárias da crista neural, as quais originam em neurônios simpáticos e apresentam como característica a imortalidade, portanto, são excelentes modelos em ensaios in vitro. Nesse sentido, o presente estudo avalia a adesão e a proliferação desta linhagem celular sobre os biopolímeros poli caprolactona (PCL) e poli L-ácido lático (PLLA). Palavras-chave: Biomateriais, PLLA, PLC, neuroblastoma, cultura. Study of Neuro2a Cells on the Biomaterials Poly L-lactic Acid and Poly CaprolactoneAbstract: Biomaterials poly L-lactic acid (PLLA) and poly caprolactone (PCL) are the most studied in the area of bioresorbable materials. Among the main features that contribute to cell interaction, we have the specific surface chemistry, electrical, hydrophobicity and topography. Also, is observed the degradation time, porosity, biocompatibility with biological tissue, as well as the preparation of the most varied shapes and sizes. The practice of cell culture, aims to study the adhesion, migration, differentiation and cell proliferation using a given material or substance. However, few studies were performed using these biomaterials and the application of neuro2A cells. It is known that this cell type is derived from the embryonic neural crest cells, which originate in sympathetic neurons and have the characteristic of immortality, therefore, are excellent models in vitro assays. Accordingly, the present study evaluates the adhesion and proliferation of this cell line on the biopolymers poly caprolactone (PCL) and poly L-lactic acid (PLLA). Glória, 187, Centro, Diamantina, MG, Brasil, Keywords: Biomaterials, PLLA, PLC, neuroblastoma, culture. Autor para correspondência: Amauri Pierucci, Departamento de Ciências Básicas, Universidade Federal dos Vales do Jequitinhonha e Mucuri -UFVJM, Rua da IntroduçãoCom o advento da bioengenharia intensificaram os estudos sobre a aplicação e ação dos biomateriais em diferentes tipos celulares. Sabe-se que a adesão, migração, diferenciação e a proliferação celular sobre determinado substrato depende em parte das propriedades intrínsecas de cada tipo celular, bem como, o tipo de material utilizado [1][2][3][4] . Dentre os produtos celulares, pode-se ressaltar a síntese de moléculas de adesã...

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The promotion of neuronal maturation on soft substrates

Cited by 172 publications

References 22 publications

Control of Neural Cell Composition in Poly(Ethylene Glycol) Hydrogel Culture with Soluble Factors

Control of Neural Cell Composition in Poly(Ethylene Glycol) Hydrogel Culture with Soluble Factors

Stochastic nanoroughness modulates neuron–astrocyte interactions and function via mechanosensing cation channels

Estudo das células Neuro2A sobre os biomateriais PCL e PLLA

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