scholarly journals Combining tissue engineering and optical imaging approaches to explore interactions along the neuro-cardiac axis

2020 ◽  
Vol 7 (6) ◽  
pp. 200265 ◽  
Author(s):  
Charalampos Sigalas ◽  
Maegan Cremer ◽  
Annika Winbo ◽  
Samuel J. Bose ◽  
Jesse L. Ashton ◽  
...  

Interactions along the neuro-cardiac axis are being explored with regard to their involvement in cardiac diseases, including catecholaminergic polymorphic ventricular tachycardia, hypertension, atrial fibrillation, long QT syndrome and sudden death in epilepsy. Interrogation of the pathophysiology and pathogenesis of neuro-cardiac diseases in animal models present challenges resulting from species differences, phenotypic variation, developmental effects and limited availability of data relevant at both the tissue and cellular level. By contrast, tissue-engineered models containing cardiomyocytes and peripheral sympathetic and parasympathetic neurons afford characterization of cellular- and tissue-level behaviours while maintaining precise control over developmental conditions, cellular genotype and phenotype. Such approaches are uniquely suited to long-term, high-throughput characterization using optical recording techniques with the potential for increased translational benefit compared to more established techniques. Furthermore, tissue-engineered constructs provide an intermediary between whole animal/tissue experiments and in silico models. This paper reviews the advantages of tissue engineering methods of multiple cell types and optical imaging techniques for the characterization of neuro-cardiac diseases.

2021 ◽  
Author(s):  
Rammohan Shukla ◽  
Nicholas D Henkel ◽  
Marissa A Smail ◽  
Xiaojun Wu ◽  
Heather A Enright ◽  
...  

We probed a transcriptomic dataset of pilocarpine-induced TLE using various ontological, machine-learning, and systems-biology approaches. We showed that, underneath the complex and penetrant changes, moderate-to-subtle upregulated homeostatic and downregulated synaptic changes associated with the dentate gyrus and hippocampal subfields could not only predict TLE but various other forms of epilepsy. At the cellular level, pyramidal neurons and interneurons showed disparate changes, whereas the proportion of non-neuronal cells increased steadily. A probabilistic Bayesian network demonstrated an aberrant and oscillating physiological interaction between oligodendrocytes and interneurons in driving seizures. Validating the Bayesian inference, we showed that the cell types driving the seizures were associated with known antiepileptic and epileptic drugs. These findings provide predictive biomarkers of epilepsy, insights into the cellular connections and causal changes associated with TLE, and a drug discovery method focusing on these events.


2000 ◽  
Vol 88 (5) ◽  
pp. 1880-1889 ◽  
Author(s):  
Navdeep S. Chandel ◽  
Paul T. Schumacker

Hypoxia elicits a variety of adaptive responses at the tissue level, at the cellular level, and at the molecular level. A physiological response to hypoxia requires the existence of an O2sensor coupled to a signal transduction system, which in turn activates the functional response. Although much has been learned about the signaling systems activated by hypoxia, no consensus exists regarding the nature of the underlying O2sensor or whether multiple sensors exist. Among previously considered mechanisms, heme proteins have been suggested to undergo allosteric modification in response to O2binding or release at different [Formula: see text] levels. Other studies suggest that ion channels may change conductance as a function of[Formula: see text], allowing them to signal the onset of hypoxia. Still other studies suggest that NADPH oxidase may decrease its generation of reactive O2species (ROS) during hypoxia. Recent data suggest that mitochondria may function as O2sensors by increasing their generation of ROS during hypoxia. These oxidant signals appear to act as second messengers in the adaptive responses to hypoxia in a variety of cell types. Such observations contribute to a growing awareness that mitochondria do more than just generate ATP, in that they initiate signaling cascades involved in adaptive responses to hypoxia and that they participate in the control of cell death pathways.


2021 ◽  
Vol 8 ◽  
Author(s):  
Kari V. Vienola ◽  
Kunal K. Dansingani ◽  
Andrew W. Eller ◽  
Joseph N. Martel ◽  
Valerie C. Snyder ◽  
...  

Torpedo maculopathy (TM) is a rare congenital defect of the retinal pigment epithelium (RPE). The RPE is often evaluated clinically using fundus autofluorescence (AF), a technique that visualizes RPE structure at the tissue level from the intrinsic AF of RPE fluorophores. TM lesions typically emit little or no AF, but this macroscopic assessment is unable to resolve the RPE cells, leaving the organization of the RPE cell mosaic in TM unknown. We used fluorescence adaptive optics scanning laser ophthalmoscopy (AOSLO) to show here for the first time the microscopic cellular-level structural alterations to the RPE cell mosaic in TM that underlie the tissue-level changes seen in conventional clinical imaging. We evaluated two patients with TM using conventional clinical imaging techniques and adaptive optics (AO) infrared autofluorescence (IRAF) in AOSLO. Confocal AOSLO revealed relatively normal cones outside the TM lesion but altered cone appearance within it and along its margins in both patients. We quantified cone topography and RPE cell morphometry from the fovea to the margin of the lesion in case 1 and found cone density to be within the normal range across the locations imaged. However, RPE morphometric analysis revealed disrupted RPE cells outside the margin of the lesion; the mean RPE cell area was greater than two standard deviations above the normative range up to approximately 1.5 mm from the lesion margin. Similar morphometric changes were seen to individual RPE cells in case 2. Multi-modal imaging with AOSLO reveals that RPE cells are abnormal in TM well beyond the margins of the characteristic TM lesion boundary defined with conventional clinical imaging. Since the TM fovea appears to be fully formed, with normal cone packing, it is possible that the congenital RPE defect in TM occurs relatively late in retinal development. This work demonstrates how cellular level imaging of the RPE can provide new insight into RPE pathologies, particularly for rare conditions such as TM.


2020 ◽  
Vol 117 (52) ◽  
pp. 32868-32879
Author(s):  
David C. Van Essen

Mechanical tension along the length of axons, dendrites, and glial processes has been proposed as a major contributor to morphogenesis throughout the nervous system [D. C. Van Essen, Nature 385, 313–318 (1997)]. Tension-based morphogenesis (TBM) is a conceptually simple and general hypothesis based on physical forces that help shape all living things. Moreover, if each axon and dendrite strive to shorten while preserving connectivity, aggregate wiring length would remain low. TBM can explain key aspects of how the cerebral and cerebellar cortices remain thin, expand in surface area, and acquire their distinctive folds. This article reviews progress since 1997 relevant to TBM and other candidate morphogenetic mechanisms. At a cellular level, studies of diverse cell types in vitro and in vivo demonstrate that tension plays a major role in many developmental events. At a tissue level, I propose a differential expansion sandwich plus (DES+) revision to the original TBM model for cerebral cortical expansion and folding. It invokes tangential tension and “sulcal zipping” forces along the outer cortical margin as well as tension in the white matter core, together competing against radially biased tension in the cortical gray matter. Evidence for and against the DES+ model is discussed, and experiments are proposed to address key tenets of the DES+ model. For cerebellar cortex, a cerebellar multilayer sandwich (CMS) model is proposed that can account for many distinctive features, including its unique, accordion-like folding in the adult, and experiments are proposed to address its specific tenets.


Author(s):  
Kartik Trehan ◽  
Christopher Yu ◽  
Sasha Bakhru ◽  
Hai-Quan Mao

Cell encapsulation in hydrogels or microcapsules is one of the approaches for providing a biomimetic microenvironment to support cell survival, proliferation and functions. Microcapsules in particular have been used to improve the mass transport properties and ease of delivery through injection. More importantly, the microenvironment in hydrogels or hydrogel microcapsules can be tailored by incorporation of relevant adhesion molecules and growth factors through chemical conjugation and physical encapsulation. These functionalized hydrogels have been shown to effectively influence cell adhesion, proliferation and differentiation. In this study, we describe the preparation and characterization of a novel hydrogel fiber by polyelectrolyte complexation. This unique fiber geometry can be useful for regeneration of cylindrical tissues and for coculture of two different cell types inside and outside the fiber membrane.


Photonics ◽  
2019 ◽  
Vol 6 (3) ◽  
pp. 98 ◽  
Author(s):  
Shi ◽  
Guan ◽  
Chen ◽  
Luo

When neuroscience’s focus moves from molecular and cellular level to systems level, information technology mixes in and cultivates a new branch neuroinformatics. Especially under the investments of brain initiatives all around the world, brain atlases and connectomics are identified as the substructure to understand the brain. We think it is time to call for a potential interdisciplinary subject, brainsmatics, referring to brain-wide spatial informatics science and emphasizing on precise positioning information affiliated to brain-wide connectome, genome, proteome, transcriptome, metabolome, etc. Brainsmatics methodology includes tracing, surveying, visualizing, and analyzing brain-wide spatial information. Among all imaging techniques, optical imaging is the most appropriate solution to achieve whole-brain connectome in consistent single-neuron resolution. This review aims to introduce contributions of optical imaging to brainsmatics studies, especially the major strategies applied in tracing and surveying processes. After discussions on the state-of-the-art technology, the development objectives of optical imaging in brainsmatics field are suggested. We call for a global contribution to the brainsmatics field from all related communities such as neuroscientists, biologists, engineers, programmers, chemists, mathematicians, physicists, clinicians, pharmacists, etc. As the leading approach, optical imaging will, in turn, benefit from the prosperous development of brainsmatics.


Author(s):  
Haijiao Liu ◽  
Craig A. Simmons ◽  
Yu Sun

Mechanical stimuli, including the elasticity of the extracellular matrix (ECM), can have profound effects on the function of cells and their responsiveness to other microenvironmental cues, thereby regulating homeostasis and disease development. For example, the response of aortic valve interstitial cells (VICs) to growth factors [1] and VIC differentiation to pathological phenotypes [2] depend on ECM elasticity. The ability of cells to sense and respond to mechanical stimuli depends on several factors, including their inherent cellular-level mechanical properties. The mechanical properties of suspended VICs [3, 4] and VICs grown on stiff glass/polystyrene [5] have been reported. However, neither of these test conditions is physiological, as VICs adhere to ECM that is orders of magnitude more compliant than glass. Some other cell types adapt their stiffness to that of their substrate [6]; we hypothesized that adherent VICs would similarly change their elasticity in response to the elastic properties of their ECM.


Plants ◽  
2019 ◽  
Vol 8 (1) ◽  
pp. 20 ◽  
Author(s):  
Emilie Aubry ◽  
Sylvie Dinant ◽  
Françoise Vilaine ◽  
Catherine Bellini ◽  
Rozenn Le Hir

Organic (e.g., sugars and amino acids) and inorganic (e.g., K+, Na+, PO42−, and SO42−) solutes are transported long-distance throughout plants. Lateral movement of these compounds between the xylem and the phloem, and vice versa, has also been reported in several plant species since the 1930s, and is believed to be important in the overall resource allocation. Studies of Arabidopsis thaliana have provided us with a better knowledge of the anatomical framework in which the lateral transport takes place, and have highlighted the role of specialized vascular and perivascular cells as an interface for solute exchanges. Important breakthroughs have also been made, mainly in Arabidopsis, in identifying some of the proteins involved in the cell-to-cell translocation of solutes, most notably a range of plasma membrane transporters that act in different cell types. Finally, in the future, state-of-art imaging techniques should help to better characterize the lateral transport of these compounds on a cellular level. This review brings the lateral transport of sugars and inorganic solutes back into focus and highlights its importance in terms of our overall understanding of plant resource allocation.


2020 ◽  
Vol 11 ◽  
Author(s):  
Patrícia A. Galletti ◽  
Marcia E. A. Carvalho ◽  
Welinton Y. Hirai ◽  
Vivian A. Brancaglioni ◽  
Valter Arthur ◽  
...  

Light-based methods are being further developed to meet the growing demands for food in the agricultural industry. Optical imaging is a rapid, non-destructive, and accurate technology that can produce consistent measurements of product quality compared to conventional techniques. In this research, a novel approach for seed quality prediction is presented. In the proposed approach two advanced optical imaging techniques based on chlorophyll fluorescence and chemometric-based multispectral imaging were employed. The chemometrics encompassed principal component analysis (PCA) and quadratic discrimination analysis (QDA). Among plants that are relevant as both crops and scientific models, tomato, and carrot were selected for the experiment. We compared the optical imaging techniques to the traditional analytical methods used for quality characterization of commercial seedlots. Results showed that chlorophyll fluorescence-based technology is feasible to discriminate cultivars and to identify seedlots with lower physiological potential. The exploratory analysis of multispectral imaging data using a non-supervised approach (two-component PCA) allowed the characterization of differences between carrot cultivars, but not for tomato cultivars. A Random Forest (RF) classifier based on Gini importance was applied to multispectral data and it revealed the most meaningful bandwidths from 19 wavelengths for seed quality characterization. In order to validate the RF model, we selected the five most important wavelengths to be applied in a QDA-based model, and the model reached high accuracy to classify lots with high-and low-vigor seeds, with a correct classification from 86 to 95% in tomato and from 88 to 97% in carrot for validation set. Further analysis showed that low quality seeds resulted in seedlings with altered photosynthetic capacity and chlorophyll content. In conclusion, both chlorophyll fluorescence and chemometrics-based multispectral imaging can be applied as reliable proxies of the physiological potential in tomato and carrot seeds. From the practical point of view, such techniques/methodologies can be potentially used for screening low quality seeds in food and agricultural industries.


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