Optimization of adhesive conditions for neural differentiation of murine embryonic stem cells using hydrogels functionalized with continuous Ile-Lys-Val-Ala-Val concentration gradients

Yang, Yueh Hsun; Khan, Zara; Ma, Cheng; Lim, Hyun Ju; Callahan, Laura A. Smith

doi:10.1016/j.actbio.2015.04.031

Cited by 39 publications

(44 citation statements)

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“…Hydrogels containing a gradient in Young's Modulus were fabricated as described in Figure , which is similar to previous descriptions . Briefly, 10% and 55% 10 kDa PEGDM solutions in PBS containing 0.1% Matrigel (BD Biosciences, San Jose, CA) and 0.1% Irgacure 2959 photoinitiator (Ciba Specialty Chemicals, Basel, Switzerland) were dispensed by two syringe pumps (New Era Pump Systems, Farmingdale, NY) running in inverse linear ramping profiles ranging from 0 to 52 mL/h [Fig.…”

Section: Experimental Methodsmentioning

confidence: 99%

“…The mechanical and material properties of the hydrogels containing a continuous gradient in Young's Modulus were determined in manner similar to previously described . Briefly, the Young's and shear moduli of the 3/8 inch disks punched down the length of hydrogels swollen in PBS overnight containing a continuous gradient in Young's Modulus [Fig.…”

Section: Experimental Methodsmentioning

confidence: 99%

“…The concentration of encapsulated proteins in the hydrogel gradients was detected using a Lowry assay as previously described on day 0, 6, and 14. Briefly, each sample was first treated with DC™ Protein Assay Reagent B (Bio‐Rad, Hercules, CA) for 30 min, followed by a 4 h incubation with Reagent A, and finally a rinse in ultrapure water.…”

Section: Experimental Methodsmentioning

confidence: 99%

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Neurite extension and neuronal differentiation of human induced pluripotent stem cell derived neural stem cells on polyethylene glycol hydrogels containing a continuous Young's Modulus gradient

Mosley

Lim

Chen

et al. 2016

J Biomedical Materials Res

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Mechanotransduction in neural cells involves multiple signaling pathways that are not fully understood. Differences in lineage and maturation state are suggested causes for conflicting reports on neural cell mechanosensitivity. To optimize matrices for use in stem cell therapy treatments transplanting human induced pluripotent stem cell derived neural stem cells (hNSC) into lesions after spinal cord injury, the effects of Young's Modulus changes on hNSC behavior must be understood. The present study utilizes polyethylene glycol hydrogels containing a continuous gradient in Young's modulus to examine changes in the Young's Modulus of the culture substrate on hNSC neurite extension and neural differentiation. Changes in the Young's Modulus of the polyethylene glycol hydrogels was found to affect neurite extension and cellular organization on the matrices. hNSC cultured on 907 Pa hydrogels were found to extend longer neurites than hNSC cultured on other tested Young's Moduli hydrogels. The gene expression of β tubulin III and microtubule-associated protein 2 in hNSC was affected by changes in the Young's Modulus of the hydrogel. The combinatory method approach used in the present study demonstrates that hNSC are mechanosensitive and the matrix Young's Modulus should be a design consideration for hNSC transplant applications. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 824-833, 2017.

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Section: Experimental Methodsmentioning

confidence: 99%

Section: Experimental Methodsmentioning

confidence: 99%

Section: Experimental Methodsmentioning

confidence: 99%

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Neurite extension and neuronal differentiation of human induced pluripotent stem cell derived neural stem cells on polyethylene glycol hydrogels containing a continuous Young's Modulus gradient

Mosley

Lim

Chen

et al. 2016

J Biomedical Materials Res

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“…An IKVAV concentration of 60 μM was optimal for 3D culture, whereas almost a 10 times higher concentration was required to achieve differentiation in 2D culture. Moreover, a concentration above the upper threshold value leads to the death of cells in 2D environments . The author suggested that low concentrations of peptide may emulate bioactive signaling and activate cellular pathways, whereas higher concentrations oversaturate the cells and block sensing mechanisms.…”

Section: Cell Culture and Differentiationmentioning

confidence: 99%

“…Moreover, a concentration above the upper threshold value leads to the death of cells in 2D environments. 28 The author suggested that low concentrations of peptide may emulate bioactive signaling and activate cellular pathways, whereas higher concentrations oversaturate the cells and block sensing mechanisms. Silk fibroin is a natural fibrous polymer with low inflammatory activity and low antigenicity.…”

Section: D Environmentmentioning

confidence: 99%

Ile‐Lys‐Val‐ala‐Val (IKVAV) peptide for neuronal tissue engineering

Patel

Santhosh

Dash

et al. 2018

Polymers for Advanced Techs

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Despite the great advances in microsurgery, some neural injuries cannot be treated surgically. Stem cell therapy is a potential approach for treating neuroinjuries and neurodegenerative disease. Researchers have developed various bioactive scaffolds for tissue engineering, exhibiting enhanced cell viability, attachment, migration, neurite elongation, and neuronal differentiation, with the aim of developing functional tissue grafts that can be incorporated in vivo. Facilitating the appropriate interactions between the cells and extracellular matrix is crucial in scaffold design. Modification of scaffolds with biofunctional motifs such as growth factors, drugs, or peptides can improve this interaction. In this review, we focus on the laminin‐derived Ile‐Lys‐Val‐Ala‐Val peptide as a biofunctional epitope for neuronal tissue engineering. Inclusion of this bioactive peptide within a scaffold is known to enhance cell adhesion as well as neuronal differentiation in both 2‐dimensional and 3‐dimensional environments. The in vivo application of this peptide is also briefly described.

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Combination of IKVAV, LRE, and GPQGIWGQ Bioactive Signaling Peptides Increases Human Induced Pluripotent Stem Cell Derived Neural Stem Cells Extracellular Matrix Remodeling and Neurite Extension

Perera¹,

Lu²,

Howell³

et al. 2020

Adv. Biosys.

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are required to understand the effects of MMP driven ECM remodeling in human systems. Although polymer [7-9] and bioactive peptide signaling [10-12] selection will alter MMP activity in the matrix, the field has traditionally focused on the use of enzymatically degradable crosslinkers to increase cellular spreading and migration by increasing pore size. [13] However, enzymatically degradable cross linkers have been found to alter cellular differentiation [14] and axonal extension in 2D culture, [15,16] which implies they have greater bioactivity than previously appreciated. To incorporate ECM remodeling as a matrix design criteria, greater consideration to the effects of all matrix components on MMP activity needs to be given. Hyaluronic acid (HA) enhances neural stem cell growth, differentiation, and axon extension. [17,18] Adding laminin to HA further increases in axon extension. [19] However, HA stimulates gelatinase (MMP 2 & 9) expression. [7,8] Gelatinase promotes axonal regeneration after CNS injury, [20] but degrades laminin. [21] Revealed cryptic sites in laminin can then participate in regulating gelatinase activity and cellular behaviors. [10,22] Use of laminin derived peptide signaling, instead of whole laminin molecules, provides more consistent bioactive signaling. Not all commonly used laminin derived peptides regulate gelatinase activity. [10,23] Laminin derived Ile-Lys-Val-Ala-Val (IKVAV) promotes neural differentiation, increases axon extension, and modulates gelatinase expression. [11,24] To further manipulate cellular responses, additional peptides are often used with IKVAV. [25] Leu-Arg-Glu (LRE), another lamininderived peptide, supports adhesion, axon guidance, and other cell behaviors not stimulated by IKVAV. [26] LRE also modulates the expression of gelatinase and inhibitors of gelatinase activity by manipulating Ca 2+ flow through Cav2.2 voltage gated Ca 2+ channels. [12] IKVAV and LRE peptide signaling in HA matrices increases protease (MMP 1 & 3) and gelatinase expression in mouse embryonic stem cells, while reducing the degradation of the HA matrix. [3] The IKVAV and LRE signaling combination is capable of affecting human induced pluripotent stem cell derived neural stem cells (hNSC) behavior in 2D culture. [27] This study examines the effect of IKVAV and LRE on hNSC,

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Optimization of adhesive conditions for neural differentiation of murine embryonic stem cells using hydrogels functionalized with continuous Ile-Lys-Val-Ala-Val concentration gradients

Cited by 39 publications

References 50 publications

Neurite extension and neuronal differentiation of human induced pluripotent stem cell derived neural stem cells on polyethylene glycol hydrogels containing a continuous Young's Modulus gradient

Neurite extension and neuronal differentiation of human induced pluripotent stem cell derived neural stem cells on polyethylene glycol hydrogels containing a continuous Young's Modulus gradient

Ile‐Lys‐Val‐ala‐Val (IKVAV) peptide for neuronal tissue engineering

Combination of IKVAV, LRE, and GPQGIWGQ Bioactive Signaling Peptides Increases Human Induced Pluripotent Stem Cell Derived Neural Stem Cells Extracellular Matrix Remodeling and Neurite Extension

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