Tissue-specific extracellular matrix accelerates the formation of neural networks and communities in a neuron-glia co-culture on a multi-electrode array

Lam, Doris; Enright, Heather A.; Cadena, José; Peters, Sandra K. G.; Sales, Ana Paula; Osburn, Joanne; Soscia, David A.; Kulp, Kristen S.; Wheeler, Elizabeth K.; Fischer, Nicholas O.

doi:10.1038/s41598-019-40128-1

Cited by 150 publications

(134 citation statements)

References 59 publications

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“…Decellularised brain ECM (an example can be seen in Fig. 1d) that are applied as substrates (either as 2D coating or 3D hydrogel) foster neurite outgrowth (Medberry et al 2013) and functional neural network formation (Lam et al 2019) better than equivalent decellularised ECM substrates from other tissues. A recent study furthermore shows that decellularised brain ECM increases the neuronal reprogramming efficiency of mouse embryonic fibroblasts into induced neurons, compared with 2D laminin-coated substrates.…”

Section: Microenvironmental Cues Influencing Neuronal Cell Developmentmentioning

confidence: 99%

Mechanotransduction in neuronal cell development and functioning

et al. 2019

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Although many details remain still elusive, it became increasingly evident in recent years that mechanosensing of microenvironmental biophysical cues and subsequent mechanotransduction are strongly involved in the regulation of neuronal cell development and functioning. This review gives an overview about the current understanding of brain and neuronal cell mechanobiology and how it impacts on neurogenesis, neuronal migration, differentiation, and maturation. We will focus particularly on the events in the cell/microenvironment interface and the decisive extracellular matrix (ECM) parameters (i.e. rigidity and nanometric spatial organisation of adhesion sites) that modulate integrin adhesion complex-based mechanosensing and mechanotransductive signalling. It will also be outlined how biomaterial approaches mimicking essential ECM features help to understand these processes and how they can be used to control and guide neuronal cell behaviour by providing appropriate biophysical cues. In addition, principal biophysical methods will be highlighted that have been crucial for the study of neuronal mechanobiology.

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Section: Microenvironmental Cues Influencing Neuronal Cell Developmentmentioning

confidence: 99%

Mechanotransduction in neuronal cell development and functioning

et al. 2019

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“…In contrast to endogenous brain regeneration, implanted cells should provide a rapid replacement of tissue and hence a site-appropriate ECM might be more important. It is noteworthy that neural stem cells in brain ECM accelerate the formation of neuronal circuitry (Lam et al, 2019).…”

Section: Cell-bioscaffolds and Engineered Micro-tissue Constructs Formentioning

confidence: 99%

Bioscaffold-Induced Brain Tissue Regeneration

Modo

2019

Front. Neurosci.

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Brain tissue lost after a stroke is not regenerated, although a repair response associated with neurogenesis does occur. A failure to regenerate functional brain tissue is not caused by the lack of available neural cells, but rather the absence of structural support to permit a repopulation of the lesion cavity. Inductive bioscaffolds can provide this support and promote the invasion of host cells into the tissue void. The putative mechanisms of bioscaffold degradation and its pivotal role to permit invasion of neural cells are reviewed and discussed in comparison to peripheral wound healing. Key differences between regenerating and non-regenerating tissues are contrasted in an evolutionary context, with a special focus on the neurogenic response as a conditio sine qua non for brain regeneration. The pivotal role of the immune system in biodegradation and the formation of a neovasculature are contextualized with regeneration of peripheral soft tissues. The application of rehabilitation to integrate newly forming brain tissue is suggested as necessary to develop functional tissue that can alleviate behavioral impairments. Pertinent aspects of brain tissue development are considered to provide guidance to produce a metabolically and functionally integrated de novo tissue. Although little is currently known about mechanisms involved in brain tissue regeneration, this review outlines the various components and their interplay to provide a framework for ongoing and future studies. It is envisaged that a better understanding of the mechanisms involved in brain tissue regeneration will improve the design of biomaterials and the methods used for implantation, as well as rehabilitation strategies that support the restoration of behavioral functions.

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“…A mitochondria-directed, cell-penetrating SSADH delivery strategy 36 might be necessary to ensure functional SSADH restoration and to avoid off-target effects. Second , cell-specific SSADH delivery might be achieved via characteristic extracellular environment of relevant cell types during development 37 . For example, since the majority of PV+ cells are enwrapped by perineuronal nets (PNN) recognized by specific proteoglycan domains 38 , enzymes or viral biomolecules packaging strategy might be designed to accommodate specific extracellular interactions to target relevant cell types.…”

Section: Discussionmentioning

confidence: 99%

Novel genetic tools to model functional enzyme restoration in succinic semialdehyde dehydrogenase deficiency (SSADHD)

Lee

Pearl

Rotenberg

2020

Preprint

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SSADHD is a rare inborn metabolic disorder caused by the functional impairment of SSADH (encoded by the aldh5a1 gene), an enzyme essential for breaking down the inhibitory neurotransmitter gamma-aminobutyric acid (GABA). In SSADHD, pathologic accumulation of GABA results in broad spectrum encephalopathy including developmental delay, ataxia, seizures and a risk of sudden unexpected death in epilepsy (SUDEP). Proof-of-concept systemic SSADH restoration via enzyme replacement therapy (ERT) or aldh5a1 gene transfer increased survival of SSADH knockout mice, suggesting that SSADH restoration might be a viable cure for SSADHD. However, before testing SSADH restoration therapy in patients, we must consider its safety and feasibility in context of the unique SSADHD pathophysiology. Specifically, a profound use-dependent down-regulation of GABA(A) receptors in SSADHD indicates a risk that sudden SSADH restoration might diminish GABAergic tone and provoke seizures. Such risk may be mitigated by gradual, rather than abrupt, SSADH restoration, or by restoration that is confined to critical cell types and brain regions. We therefore describe early work to construct a novel SSADHD mouse model that allows 'on-demand' SSADH restoration for the systematic investigation of the rate, timing and cell-specific parameters of SSADH-restoring therapies. We aim to understand the clinical readiness of specific SSADH restoration protocols on brain physiology for purposes of accelerating the bench to bed-side development of ERT or gene therapy for SSADHD patients.

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Tissue-specific extracellular matrix accelerates the formation of neural networks and communities in a neuron-glia co-culture on a multi-electrode array

Cited by 150 publications

References 59 publications

Mechanotransduction in neuronal cell development and functioning

Mechanotransduction in neuronal cell development and functioning

Bioscaffold-Induced Brain Tissue Regeneration

Novel genetic tools to model functional enzyme restoration in succinic semialdehyde dehydrogenase deficiency (SSADHD)

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