Tissue engineering the monosynaptic circuit of the stretch reflex arc with co-culture of embryonic motoneurons and proprioceptive sensory neurons

Guo, Xiufang; Ayala, Jennifer; González, Mercedes Freire; Stancescu, Maria; Lambert, Stephen; Hickman, James J.

doi:10.1016/j.biomaterials.2012.04.042

Cited by 20 publications

(23 citation statements)

References 72 publications

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“…These neurons tended to form clusters with their axons aligning uniformly and were located between the clustered cell bodies (Figure 2C). This feature has also been observed in cell cultures derived from rat embryonic DRGs in which sensory neurons formed clusters with their axons developing “highway” bundles traveling between individual clusters (Figure 2D) [32]. …”

Section: Resultssupporting

confidence: 61%

Derivation of sensory neurons and neural crest stem cells from human neural progenitor hNP1

et al. 2013

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Although sensory neurons constitute a critical component for the proper function of the nervous system, the in vitro differentiation of functional sensory neurons from human stem cells has not yet been reported. This study presents the differentiation of sensory neurons (SNs) from a human neural progenitor cell line, hNP1, and their functional maturation in a defined, in vitro culture system without murine cell feeder layers. The SNs were characterized by immunocytochemistry and their functional maturation was evaluated by electrophysiology. Neural crest (NC) precursors, as one of the cellular derivatives in the differentiation culture, were isolated, propagated, and tested for their ability to generate sensory neurons. The hSC-derived SNs, as well as the NC precursors provide valuable tools for developing in vitro functional systems that model sensory neuron-related neural circuits and for designing therapeutic models for related diseases.

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Section: Resultssupporting

confidence: 61%

Derivation of sensory neurons and neural crest stem cells from human neural progenitor hNP1

et al. 2013

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“…This has led to defined systems for cardiac (Das et al, 2004; Natarajan et al, 2011), muscle (Das et al, 2006; Das et al, 2009), NMJ formation (Das et al, 2010; Guo et al, 2011; Guo et al, 2010a), sensory neurons and motoneuron co-culture (Das et al, 2007; Davis et al, 2012a) as well as for human stem cell derived culture models (Davis et al, 2012b; Guo et al, 2012; Guo et al, 2010b). The similar media system, non-biological substrate and defined cell preparation has enabled the integration of these models for body-on-a-chip applications.…”

Section: Introductionmentioning

confidence: 99%

Myelination and node of Ranvier formation on sensory neurons in a defined in vitro system

Rumsey

McAleer

Das

et al. 2013

In Vitro Cell.Dev.Biol.-Animal

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One of the most important developmental modifications of the nervous system is Schwann cell myelination of axons. Schwann cells ensheath axons to create myelin segments to provide protection to the axon as well as increase the conduction of action potentials. In vitro neuronal systems provide a unique modality to study a variety of factors influencing myelination as well as diseases associated with myelin sheath degradation. This work details the development of a patterned in vitro myelinating dorsal root ganglion culture. This defined system utilized a serum-free medium in combination with a patterned substrate, utilizing the cytophobic and cytophilic molecules (poly)ethylene glycol (PEG) and N-1[3 (trimethoxysilyl) propyl] diethylenetriamine (DETA), respectively. Directional outgrowth of the neurites and subsequent myelination was controlled by surface modifications, and conformity to the pattern was measured over the duration of the experiments. The myelinated segments and nodal proteins were visualized and quantified using confocal microscopy. This tissue-engineered system provides a highly controlled, reproducible model for studying Schwann cell interactions with sensory neurons, as well as the myelination process, and its effect on neuronal plasticity and peripheral nerve regeneration. It is also compatible for use in bio-hybrid constructs to reproduce the stretch reflex arc on a chip because the media combination used is the same we have used previously for motoneurons, muscle and for neuromuscular junction (NMJ) formation. This work could have application for the study of demyelinating diseases such as diabetes induced peripheral neuropathy and could rapidly translate to a role in the discovery of drugs promoting enhanced peripheral nervous system (PNS) remyelination.

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“…152 Establishment of an in vitro reex arc would be an invaluable tool for both basic and applied biomedical research, and has so far generated a series of in vitro biological systems using either primary rat cells or human stem cell-derived components. 9,[152][153][154] Blood-brain barrier: The blood-brain barrier (BBB) is a biological construct that selectively restricts the passage of blood-derived substances to the CNS, and plays a critical role in maintaining CNS homeostasis and neuronal function. The BBB consists primarily of three cell types: microvascular endothelial cells on the luminal side of the vascular wall, and pericytes and astrocytes (glial cells) lining the extra-luminal surface.…”

Section: Central Nervous System (Cns)/peripheral Nervous System (Pns)mentioning

confidence: 99%

‘Body-on-a-Chip’ Technology and Supporting Microfluidics

Smith¹,

Long²,

McAleer³

et al. 2014

Human-Based Systems for Translational Research

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In order to effectively streamline current drug development protocols, there is a need to generate high information content preclinical screens capable of generating data with a predictive power in relation to the activity of novel therapeutics in humans. Given the poor predictive power of animal models, and the lack of complexity and interconnectivity of standard in vitro culture methodologies, many investigators are now moving toward the development of physiologically and functionally accurate culture platforms composed of human cells to investigate cellular responses to drug compounds in high-throughput preclinical studies. The generation of complex, multi-organ in vitro platforms, built to recapitulate physiological dimensions, flow rates and shear stresses, is being investigated as the logical extension of this drive. Production and application of a biologically accurate multi-organ platform, or ‘body-on-a-chip’, would facilitate the correct modelling of the dynamic and interconnected state of living systems for high-throughput drug studies as well as basic and applied biomolecular research. This chapter will discuss current technologies aimed at producing ‘body-on-a-chip’ models, as well as highlighting recent advances and important challenges still to be met in the development of biomimetic single-organ systems for drug development purposes.

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Tissue engineering the monosynaptic circuit of the stretch reflex arc with co-culture of embryonic motoneurons and proprioceptive sensory neurons

Cited by 20 publications

References 72 publications

Derivation of sensory neurons and neural crest stem cells from human neural progenitor hNP1

Derivation of sensory neurons and neural crest stem cells from human neural progenitor hNP1

Myelination and node of Ranvier formation on sensory neurons in a defined in vitro system

‘Body-on-a-Chip’ Technology and Supporting Microfluidics

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