Bifunctional Hydrogels Containing the Laminin Motif IKVAV Promote Neurogenesis

Farrukh, Aleeza; Ortega, Felipe; Fan, Wenqiang; Marichal, Nicolás; Paez, Julieta I.; Berninger, Benedikt; Campo, Aránzazu del; Salierno, Marcelo

doi:10.1016/j.stemcr.2017.09.002

Cited by 102 publications

(84 citation statements)

References 33 publications

(42 reference statements)

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“…Inclusion of IKVAV has also been reported to reduce astrogliosis after injury . In vitro , IKVAV‐bearing hydrogels are reported to promote differentiation of neurons while reducing differentiation of astrocytes . YIGSR has also been reported to support survival and neurogenesis of transplanted NS/PCs and has been widely found to promote neurite extension .…”

Section: Discussionmentioning

confidence: 99%

“…100,101 In vitro, IKVAV-bearing hydrogels are reported to promote differentiation of neurons while reducing differentiation of astrocytes. 102,103 YIGSR has also been reported to support survival and neurogenesis of transplanted NS/PCs 104 and has been widely found to promote neurite extension. 105,106 YIGSR and IKVAV are known to synergistically improve neurite attachment and outgrowth.…”

Section: Discussionmentioning

confidence: 99%

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Peptide‐modified, hyaluronic acid‐based hydrogels as a 3D culture platform for neural stem/progenitor cell engineering

Seidlits

Liang

Bierman

et al. 2019

J Biomedical Materials Res

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Neural stem/progenitor cell (NS/PC)‐based therapies have shown exciting potential for regeneration of the central nervous system (CNS) and NS/PC cultures represent an important resource for disease modeling and drug screening. However, significant challenges limiting clinical translation remain, such as generating large numbers of cells required for model cultures or transplantation, maintaining physiologically representative phenotypes ex vivo and directing NS/PC differentiation into specific fates. Here, we report that culture of human NS/PCs in 3D, hyaluronic acid (HA)‐rich biomaterial microenvironments increased differentiation toward oligodendrocytes and neurons over 2D cultures on laminin‐coated glass. Moreover, NS/PCs in 3D culture exhibited a significant reduction in differentiation into reactive astrocytes. Many NS/PC‐derived neurons in 3D, HA‐based hydrogels expressed synaptophysin, indicating synapse formation, and displayed electrophysiological characteristics of immature neurons. While inclusion of integrin‐binding, RGD peptides into hydrogels resulted in a modest increase in numbers of viable NS/PCs, no combination of laminin‐derived, adhesive peptides affected differentiation outcomes. Notably, 3D cultures of differentiating NS/PCs were maintained for at least 70 days in medium with minimal growth factor supplementation. In sum, results demonstrate the use of 3D, HA‐based biomaterials for long‐term expansion and differentiation of NS/PCs toward oligodendroglial and neuronal fates, while inhibiting astroglial fates. © 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 107A: 704–718, 2019.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Peptide‐modified, hyaluronic acid‐based hydrogels as a 3D culture platform for neural stem/progenitor cell engineering

Seidlits

Liang

Bierman

et al. 2019

J Biomedical Materials Res

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“…14 In contrast to the MGC-RGD and MGC hydrogels, ASC viability was significantly lower in the MGC-IKVAV hydrogel group at all time points, with a significant decrease in cell viability over time. Previous studies of this 19-mer IKVAV peptide sequence have predominantly focused on cells cultured on peptide-modified 2-D surfaces, 24,25,56 and cellular interactions with the peptide may be substantially altered within a 3-D microenvironment. 57 Further, the response with the ASCs may be cell-type dependent, as this IKVAV sequence has been primarily studied with neural cell populations.…”

Section: Discussionmentioning

confidence: 99%

Peptide‐modified methacrylated glycol chitosan hydrogels as a cell‐viability supporting pro‐angiogenic cell delivery platform for human adipose‐derived stem/stromal cells

Dhillon

Young

Sherman

et al. 2018

J Biomedical Materials Res

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Cell‐based therapies involving the injection of adipose‐derived stem/stromal cells (ASCs) within rationally designed biomaterials are a promising approach for stimulating angiogenesis. With this focus, the current work explored the effects of incorporating integrin‐binding RGD or IKVAV peptides within in situ‐gelling N‐methacrylate glycol chitosan (MGC) hydrogels on the response of encapsulated human ASCs. Initial studies focused on hydrogel characterization to validate that the MGC, MGC‐RGD, and MGC‐IKVAV hydrogels had similar biomechanical properties. ASC viability following encapsulation and culture under 2% O2 was significantly impaired in the MGC‐IKVAV group relative to the MGC and MGC‐RGD groups. In contrast, sustained viability, along with enhanced cell spreading and metabolic activity were observed in the MGC‐RGD group. Investigation of angiogenic transcription suggested that the incorporation of the peptide groups did not substantially alter the pro‐angiogenic gene expression profile of the encapsulated ASCs after 7 days of culture under 2% O2. Consistent with the in vitro findings, preliminary in vivo characterization following subcutaneous implantation into NOD/SCID mice showed that ASC retention was enhanced in the MGC‐RGD hydrogels relative to the MGC‐IKVAV group at 14 days. Further, the encapsulated ASCs in the MGC and MGC‐RGD groups promoted murine CD31+ endothelial cell recruitment to the peri‐implant region. Overall, the results indicate that the MGC‐RGD and MGC hydrogels are promising platforms for ASC delivery, and suggest that strategies that support long‐term ASC viability can augment in vivo angiogenesis through paracrine mechanisms. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 107A: 571–585, 2019.

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“…The REDV sequence from fibronectin is a cell adhesion motif to integrin α 4 β 1 , selective for the endothelial cells (Mould et al, 1991;Massia and Hubbell, 1992). Owing to the specificity toward endothelial cells, the REDV sequence has been modified on the system to transport gene to vascular endothelial cells Zhou et al, 2016) In addition, the active peptide sequences from laminin are able to interact with integrins, syndecans, α-dystroglycan, and CD44, to perform various biological activities, cell adhesion and neurite outgrowth and proliferation, and angiogenesis, such as those mediated by laminin (Farrukh et al, 2017). The YIGSR sequence and IKVAV sequence from laminin are also cell adhesion domains (Graf et al, 1987;Tashiro et al, 1989), and the RKRLQVQLSIRT (AG73) sequence derived from the mouse laminin α1 chain interacts with syndecans to promote cell adhesion, neurite outgrowth, and angiogenesis (Hoffman et al, 2001).…”

Section: Interactions Of Ecm With Cell Receptorsmentioning

confidence: 99%

Targeted Drug Delivery via the Use of ECM-Mimetic Materials

Hwang

Sullivan

Kiick

2020

Front. Bioeng. Biotechnol.

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The use of drug delivery vehicles to improve the efficacy of drugs and to target their action at effective concentrations over desired periods of time has been an active topic of research and clinical investigation for decades. Both synthetic and natural drug delivery materials have facilitated locally controlled as well as targeted drug delivery. Extracellular matrix (ECM) molecules have generated widespread interest as drug delivery materials owing to the various biological functions of ECM. Hydrogels created using ECM molecules can provide not only biochemical and structural support to cells, but also spatial and temporal control over the release of therapeutic agents, including small molecules, biomacromolecules, and cells. In addition, the modification of drug delivery carriers with ECM fragments used as cell-binding ligands has facilitated celltargeted delivery and improved the therapeutic efficiency of drugs through interaction with highly expressed cellular receptors for ECM. The combination of ECM-derived hydrogels and ECM-derived ligand approaches shows synergistic effects, leading to a great promise for the delivery of intracellular drugs, which require specific endocytic pathways for maximal effectiveness. In this review, we provide an overview of cellular receptors that interact with ECM molecules and discuss examples of selected ECM components that have been applied for drug delivery in both local and systemic platforms. Finally, we highlight the potential impacts of utilizing the interaction between ECM components and cellular receptors for intracellular delivery, particularly in tissue regeneration applications.

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Bifunctional Hydrogels Containing the Laminin Motif IKVAV Promote Neurogenesis

Cited by 102 publications

References 33 publications

Peptide‐modified, hyaluronic acid‐based hydrogels as a 3D culture platform for neural stem/progenitor cell engineering

Peptide‐modified, hyaluronic acid‐based hydrogels as a 3D culture platform for neural stem/progenitor cell engineering

Peptide‐modified methacrylated glycol chitosan hydrogels as a cell‐viability supporting pro‐angiogenic cell delivery platform for human adipose‐derived stem/stromal cells

Targeted Drug Delivery via the Use of ECM-Mimetic Materials

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