scholarly journals A 3D disease and regeneration model of peripheral nervous system–on–a–chip

2021 ◽  
Vol 7 (5) ◽  
pp. eabd9749
Author(s):  
Sujin Hyung ◽  
Seung-Ryeol Lee ◽  
Jiho Kim ◽  
Youngtaek Kim ◽  
Suryong Kim ◽  
...  

Demyelinating diseases involve loss of myelin sheaths and eventually lead to neurological problems. Unfortunately, the precise mechanisms remain unknown, and there are no effective therapies. To overcome these limitations, a reliable and physiologically relevant in vitro model is required. Here, we present a three-dimensional peripheral nervous system (PNS) microfluidic platform that recapitulates the full spectrum of myelination, demyelination, and remyelination using primary Schwann cells (SCs) and motor neurons (MNs). The platform enables reproducible hydrogel patterning and long-term stable coculture of MNs and SCs over 40 days in vitro based on three distinct design factors. Furthermore, the on-demand detachable substrate allows in-depth biological analysis. We demonstrated the possibility of mimicking segmental demyelination by lysophosphatidylcholine, and recovery of myelin structure by application of two drugs: benzatropine or methylcobalamin. This 3D PNS disease–on–a–chip may serve as a potential platform for understanding the pathophysiology of demyelination and screening drugs for remyelination.


2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Sunghee Estelle Park ◽  
Jinchul Ahn ◽  
Hyo-Eun Jeong ◽  
Inchan Youn ◽  
Dongeun Huh ◽  
...  

AbstractRecent advances in three-dimensional (3D) cell culture models developed on organ-on-a-chip or microfluidic devices have shown their capability to recapitulate the in vivo microenvironment as well as their potential as tools in biomedical research. Here, we present an in vitro model of the peripheral nervous system (PNS) by establishing a coculture model of motor neurons (MNs) and Schwann cells (SCs) in a 3D environment in a microengineered extracellular matrix hydrogel scaffold. The collagen scaffold placed at the center of the microdevice provided a 3D cellular microenvironment where the axons of MNs were allowed to actively interact with SCs during their growth and maturation. By treating the MN–SC coculture model with ascorbic acid, we were able to model the myelination process in the PNS, which was evidenced by the increased expression of myelin markers in SCs. Moreover, we show that this can be reversed by treating myelinated nerve fibers with glial growth factor (neuregulin-1 isoform) to potentially block the formation of the myelin sheath and induce demyelination. Our 3D cell culture model may be used to achieve active control of the myelinating and demyelinating processes in the PNS and thus may offer new opportunities to study pathophysiological processes involved in motor neuron diseases by in vitro modeling.



2021 ◽  
Vol 11 (20) ◽  
pp. 9485
Author(s):  
Paolo Raffa ◽  
Maria Easler ◽  
Francesca Cecchinato ◽  
Beatrice Auletta ◽  
Valentina Scattolini ◽  
...  

Decellularized skeletal muscle (dSkM) constructs have received much attention in recent years due to the versatility of their applications in vitro. In search of adequate in vitro models of the skeletal muscle tissue, the dSkM offers great advantages in terms of the preservation of native-tissue complexity, including three-dimensional organization, the presence of residual signaling molecules within the construct, and their myogenic and neurotrophic abilities. Here, we attempted to develop a 3D model of neuromuscular tissue. To do so, we repopulated rat dSkM with human primary myogenic cells along with murine fibroblasts and we coupled them with organotypic rat spinal cord samples. Such culture conditions not only maintained multiple cell type viability in a long-term experimental setup, but also resulted in functionally active construct capable of contraction. In addition, we have developed a customized culture system which enabled easy access, imaging, and analysis of in vitro engineered co-cultures. This work demonstrates the ability of dSkM to support the development of a contractile 3D in vitro model of neuromuscular tissue fit for long-term experimental evaluations.



2011 ◽  
Vol 27 (2) ◽  
pp. 229-233
Author(s):  
Katrin Sabine Blum ◽  
Christian Hagel ◽  
Eva Neuen-Jacob ◽  
Peter Herkenrath ◽  
Jens Fiehler ◽  
...  




1989 ◽  
Vol 61 (4) ◽  
pp. 833-844 ◽  
Author(s):  
P. S. Dickinson ◽  
E. Marder

1. The cardiac sac motor pattern consists of slow and irregular impulse bursts in the motor neurons [cardiac sac dilator 1 and 2 (CD1 and CD2)] that innervate the dilator muscles of the cardiac sac region of the crustacean foregut. 2. The effects of the peptides, proctolin and red pigment-concentrating hormone (RPCH), on the cardiac sac motor patterns produced by in vitro preparations of the combined stomatogastric nervous system [the stomatogastric ganglion (STG), the paired commissural ganglia (CGs), and the oesophageal ganglion (OG)] were studied. 3. Bath applications of either RPCH or proctolin activated the cardiac sac motor pattern when this motor pattern was not already active and increased the frequency of the cardiac sac motor pattern in slowly active preparations. 4. The somata of CD1 and CD2 are located in the esophageal and stomatogastric ganglia, respectively. Both neurons project to all four of the ganglia of the stomatogastric nervous system. RPCH elicited cardiac sac motor patterns when applied to any region of the stomatogastric nervous system, suggesting a distributed pattern generating network with multiple sites of modulation. 5. The anterior median (AM) neuron innervates the constrictor muscles of the cardiac sac. The AM usually functions as a part of the gastric mill pattern generator. However, when the cardiac sac is activated by RPCH applied to the stomatogastric ganglion, the AM neuron becomes active in antiphase with the cardiac sac dilator bursts. This converts the cardiac sac motor pattern from a one-phase rhythm to a two-phase rhythm. 6. These data show that a neuropeptide can cause a neuronal element to switch from being solely a component of one neuronal circuit to functioning in a second one as well. This example shows that peptidergic "reconfiguration" of neuronal networks can produce substantial changes in the behavior of associated neurons.



Lab on a Chip ◽  
2017 ◽  
Vol 17 (20) ◽  
pp. 3447-3461 ◽  
Author(s):  
Gaurav Agrawal ◽  
Aereas Aung ◽  
Shyni Varghese

We introduce a microfluidic platform in which we culture three-dimensional skeletal muscle tissues, while evaluating tissue formation and toxin-induced muscle injury.



2007 ◽  
Vol 27 (2_suppl) ◽  
pp. 110-115 ◽  
Author(s):  
Susan Yung ◽  
Chan Tak Mao

♦ Background The introduction of peritoneal dialysis (PD) as a modality of renal replacement therapy has provoked much interest in the biology of the peritoneal mesothelial cell. Mesothelial cells isolated from omental tissue have immunohistochemical markers that are identical to those of mesothelial stem cells, and omental mesothelial cells can be cultivated in vitro to study changes to their biologic functions in the setting of PD. ♦ Method The present article describes the structure and function of mesothelial cells in the normal peritoneum and details the morphologic changes that occur after the introduction of PD. Furthermore, this article reviews the literature of mesothelial cell culture and the limitations of in vitro studies. ♦ Results The mesothelium is now considered to be a dynamic membrane that plays a pivotal role in the homeostasis of the peritoneal cavity, contributing to the control of fluid and solute transport, inflammation, and wound healing. These functional properties of the mesothelium are compromised in the setting of PD. Cultures of peritoneal mesothelial cells from omental tissue provide a relevant in vitro model that allows researchers to assess specific molecular pathways of disease in a distinct population of cells. Structural and functional attributes of mesothelial cells are discussed in relation to long-term culture, proliferation potential, age of tissue donor, use of human or animal in vitro models, and how the foregoing factors may influence in vitro data. ♦ Conclusions The ability to propagate mesothelial cells in culture has resulted, over the past two decades, in an explosion of mesothelial cell research pertaining to PD and peritoneal disorders. Independent researchers have highlighted the potential use of mesothelial cells as targets for gene therapy or transplantation in the search to provide therapeutic strategies for the preservation of the mesothelium during chemical or bacterial injury.



2004 ◽  
Vol 77 (5) ◽  
pp. 662-669 ◽  
Author(s):  
Ravi J. Tolwani ◽  
Jos� M. Cosgaya ◽  
Sushama Varma ◽  
Reza Jacob ◽  
Lydia E. Kuo ◽  
...  


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