Engineering hydrogels with affinity-bound laminin as 3D neural stem cell culture systems

Barros, Daniela; Conde-Sousa, Eduardo; Gonçalves, Andreia M.; Han, Woojin M.; Garcı́a, Andrés J.; Amaral, Isabel F.; Pêgo, Ana Paula

doi:10.1039/c9bm00348g

Cited by 39 publications

(39 citation statements)

References 47 publications

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“…The use of hydrogels for neural cell applications, i.e., neuronal tissue regeneration, has been reviewed previously [ 61 ], identifying various LAM-modified hydrogels [ 55 , 62 , 63 , 64 ] among other modifications to be promising matrices for the promotion of neurite outgrowth, a process which is necessary for neuronal network formation. Exemplary, hyaluronic acid-laminin hydrogels facilitate in vivo migration of neural progenitor/stem cells (NPSC) [ 65 ].…”

Section: Discussionmentioning

confidence: 99%

Neuronal Differentiation from Induced Pluripotent Stem Cell-Derived Neurospheres by the Application of Oxidized Alginate-Gelatin-Laminin Hydrogels

et al. 2021

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Biodegradable hydrogels that promote stem cell differentiation into neurons in three dimensions (3D) are highly desired in biomedical research to study drug neurotoxicity or to yield cell-containing biomaterials for neuronal tissue repair. Here, we demonstrate that oxidized alginate-gelatin-laminin (ADA-GEL-LAM) hydrogels facilitate neuronal differentiation and growth of embedded human induced pluripotent stem cell (hiPSC) derived neurospheres. ADA-GEL and ADA-GEL-LAM hydrogels exhibiting a stiffness close to ~5 kPa at initial cell culture conditions of 37 °C were prepared. Laminin supplemented ADA-GEL promoted an increase in neuronal differentiation in comparison to pristine ADA-GEL, with enhanced neuron migration from the neurospheres to the bulk 3D hydrogel matrix. The presence of laminin in ADA-GEL led to a more than two-fold increase in the number of neurospheres with migrated neurons. Our findings suggest that laminin addition to oxidized alginate—gelatin hydrogel matrices plays a crucial role to tailor oxidized alginate-gelatin hydrogels suitable for 3D neuronal cell culture applications.

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Section: Discussionmentioning

confidence: 99%

Neuronal Differentiation from Induced Pluripotent Stem Cell-Derived Neurospheres by the Application of Oxidized Alginate-Gelatin-Laminin Hydrogels

et al. 2021

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“…The initial mesh size of 10.5 ± 0.9 nm is sufficient to allow the diffusion of smaller metabolites, however, may restrict the movement of larger molecules such as enzymes, growth factors and ECM components. Furthermore, small mesh sizes have been demonstrated to limit the capacity for cellular interaction and migration (Koshy et al, 2016;Barros et al, 2019). In fact, past studies have found that deposition of ECM components by encapsulated cells was localized to the immediate vicinity of the cell surface (Aregueta-Robles et al, 2015;Goding et al, 2017), correlating with the low mesh size measured for the encapsulating hydrogel.…”

Section: Discussionmentioning

confidence: 99%

Hydrogels for 3D Neural Tissue Models: Understanding Cell-Material Interactions at a Molecular Level

Vallejo-Giraldo

Genta

Cauvi

et al. 2020

Front. Bioeng. Biotechnol.

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The development of 3D neural tissue analogs is of great interest to a range of biomedical engineering applications including tissue engineering of neural interfaces, treatment of neurodegenerative diseases and in vitro assessment of cell-material interactions. Despite continued efforts to develop synthetic or biosynthetic hydrogels which promote the development of complex neural networks in 3D, successful long-term 3D approaches have been restricted to the use of biologically derived constructs. In this study a poly (vinyl alcohol) biosynthetic hydrogel functionalized with gelatin and sericin (PVA-SG), was used to understand the interplay between cell-cell communication and cell-material interaction. This was used to probe critical shortterm interactions that determine the success or failure of neural network growth and ultimately the development of a useful model. Complex primary ventral mesencephalic (VM) neural cells were encapsulated in PVA-SG hydrogels and critical molecular cues that demonstrate mechanosensory interaction were examined. Neuronal presence was constant over the 10 day culture, but the astrocyte population decreased in number. The lack of astrocytic support led to a reduction in neural process outgrowth from 24.0 ± 1.3 µm on Day 7 to 7.0 ± 0.1 µm on Day 10. Subsequently, purified astrocytes were studied in isolation to understand the reasons behind PVA-SG hydrogel inability to support neural network development. It was proposed that the spatially restrictive nature (or tight mesh size) of PVA-SG hydrogels limited the astrocytic actin polymerization together with a cytoplasmic-nuclear translocation of YAP over time, causing an alteration in their cell cycle. This was confirmed by the evaluation of p27 /Kip1 gene that was found to be upregulated by a twofold increase in expression at both Days 7 and 10 compared to Day 3, indicating the quiescent stage of the astrocytes in PVA-SG hydrogel. Cell migration was further studied by the quantification of MMP-2 production that was negligible compared to 2D controls, ranging from 2.7 ± 2.3% on Day 3 to 5.3 ± 2.9% on Day 10. This study demonstrates the importance of understanding astrocyte-material interactions at the molecular level, with the need to address spatial constraints in the 3D hydrogel environment. These findings will inform the design of future hydrogel constructs with greater capacity for remodeling by the cell population to create space for cell migration and neural process extension.

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“…(115−119) Indeed, this is evident in some of the studies reported in Table 1, which point out that the immobilization approach significantly affects laminin function. (116,118,119) Strategies explored to date, for full-length laminin immobilization have relied either on its transient noncovalent incorporation or physical entrapment (109,120−122) or, alternatively, on its nonselective covalent immobilization (110,111,115−117,120,123−126) by taking advantage of functional groups present in multiple sites of the laminin structure, such as amines and thiols (see Figure 5 for illustrative examples based on PEG hydrogels). While physical entrapment ensures no conformational changes of the protein due to Version: Postprint (identical content as published paper) This is a self-archived document from i3S -Instituto de Investigação e Inovação em Saúde in the University of Porto Open Repository For Open Access to more of our publications, please visit http://repositorio-aberto.up.pt/ A01/00 chemical conjugation, the absence of a stable binding may allow protein release by diffusion, especially in noncovalently cross-linked hydrogels.…”

Section: Hydrogels Functionalized With Full-length Lamininmentioning

confidence: 99%

“…Moreover, we showed the potential of affinity-bound laminin synthetic hydrogels, to be used as a dynamic 3D platform enabling human NSC proliferation, neuronal differentiation, and neurite extension. (119) Laminin-111 purified from Engelbreth-Holm-Swarm mouse sarcoma cells has been, to the best of our knowledge, the isoform of choice for the development of laminin-inspired hydrogels (Table 1). Accordingly, the putative immune reaction against laminin is a key issue to be considered when envisaging the use of this ECM protein for the development of cell-instructive hydrogels.…”

Section: Conclusion and Future Perspectivesmentioning

confidence: 99%

Laminin-Inspired Cell-Instructive Microenvironments for Neural Stem Cells

2019

Self Cite

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Laminin is a heterotrimeric glycoprotein with a key role in the formation and maintenance of the basement membrane architecture and properties, as well as on the modulation of several biological functions, including cell adhesion, migration, differentiation and matrix-mediated signaling. In the central nervous system (CNS), laminin is differentially expressed during development and homeostasis, with an impact on the modulation of cell function and fate. Within neurogenic niches, laminin is one of the most important and well described extracellular matrix (ECM) proteins. Specifically, efforts have been made to understand laminin assembly, domain architecture, and interaction of its different bioactive domains with cell surface receptors, soluble signaling molecules, and ECM proteins, to gain insight into the role of this ECM protein and its receptors on the modulation of neurogenesis, both in homeostasis and during repair. This is also expected to provide a rational basis for the design of biomaterial-based matrices mirroring the biological properties of the basement membrane of neural stem cell niches, for application in neural tissue repair and cell transplantation. This review provides a general overview of laminin structure and domain architecture, as well as the main biological functions mediated by this heterotrimeric glycoprotein. The expression and distribution of laminin in the CNS and, more specifically, its role within adult neural stem cell niches is summarized. Additionally, a detailed overview on the use of full-length laminin and laminin derived peptide/recombinant laminin fragments for the development of hydrogels for mimicking the neurogenic niche microenvironment is given. Finally, the main challenges associated with the development of laminin-inspired hydrogels and the hurdles to overcome for these to progress from bench to bedside are discussed. Version: Postprint (identical content as published paper) This is a self-archived document from i3S -Instituto de Investigação e Inovação em Saúde in the University of Porto Open Repository For Open Access to more of our publications, please visit http://repositorio-aberto.up.pt/ A01/00 Version: Postprint (identical content as published paper) This is a self-archived document from i3S -Instituto de Investigação e Inovação em Saúde in the University of Porto Open Repository For Open Access to more of our publications, please visit http://repositorio-aberto.up.pt/ A01/00 Version: Postprint (identical content as published paper) This is a self-archived document from i3S -Instituto de Investigação e Inovação em Saúde in the University of Porto Open Repository For Open Access to more of our publications, please visit http://repositorio-aberto.up.pt/ A01/00 which is divided into five laminin globular (LG) domains (LG1-LG5) grouped into functional and structural distinct subdomains, LG1-3 and LG4 and LG5.(23) The coiled-coil is thought to help to orientate the LG domains so that they can be available to interact with cells via cell surface receptors, including...

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Engineering hydrogels with affinity-bound laminin as 3D neural stem cell culture systems

Abstract: Degradable synthetic hydrogels with site-selective immobilized laminin constitute attractive platforms for hNSC culture in 3D or for cell transplantation.

Cited by 39 publications

References 47 publications

Neuronal Differentiation from Induced Pluripotent Stem Cell-Derived Neurospheres by the Application of Oxidized Alginate-Gelatin-Laminin Hydrogels

Neuronal Differentiation from Induced Pluripotent Stem Cell-Derived Neurospheres by the Application of Oxidized Alginate-Gelatin-Laminin Hydrogels

Hydrogels for 3D Neural Tissue Models: Understanding Cell-Material Interactions at a Molecular Level

Laminin-Inspired Cell-Instructive Microenvironments for Neural Stem Cells

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