Development of a Novel Model System to Study Remodeling of ECM Scaffolds in Response to Cyclic Stretching

2003 ◽  
Author(s):  
Thomas W. Gilbert ◽  
James H.-C. Wang ◽  
Stephen F. Badylak ◽  
Savio L.-Y. Woo
Keyword(s):  
Mechanical Load ◽  
Complex Loading ◽  
Biological Tissues ◽  
In Vitro Models ◽  
Matrix Remodeling ◽  
Cyclic Stretching ◽  
A Cell ◽  
Cyclic Mechanical Load

In an effort to better understand the role of mechanical loading on the healing and remodeling of biological tissues, a number of in vitro models have been developed to apply either static or cyclic mechanical load to cell-seeded scaffolds (Huang 1993, Langelier 1999, Cacou 2000). The current study describes the validation of a new system designed to facilitate the study of matrix remodeling in cell seeded scaffolds, as well as the formation of tissue engineered scaffolds for potential use in repair of healing ligaments and tendons. Our objective was to develop a system that would allow a cell seeded scaffold to remain viable under cyclic loading for long periods of time, with the capability to apply complex loading regimes to the scaffold while monitoring the load in the scaffold.

Bioengineered in vitro Vascular Models for Applications in Interventional Radiology

2019 ◽  
Vol 24 (45) ◽  
pp. 5367-5374 ◽  
Author(s):  
Xiaoyun Li ◽  
Seyed M. Moosavi-Basri ◽  
Rahul Sheth ◽  
Xiaoying Wang ◽  
Yu S. Zhang
Keyword(s):  
Interventional Radiology ◽  
Animal Models ◽  
Blood Vessels ◽  
In Vitro Models ◽  
The Past ◽  
Endovascular Interventions ◽  
Conventional Animal ◽  
Vascular Structures

The role of endovascular interventions has progressed rapidly over the past several decades. While animal models have long-served as the mainstay for the advancement of this field, the use of in vitro models has become increasingly widely adopted with recent advances in engineering technologies. Here, we review the strategies, mainly including bioprinting and microfabrication, which allow for fabrication of biomimetic vascular models that will potentially serve to supplement the conventional animal models for convenient investigations of endovascular interventions. Besides normal blood vessels, those in diseased states, such as thrombosis, may also be modeled by integrating cues that simulate the microenvironment of vascular disorders. These novel engineering strategies for the development of biomimetic in vitro vascular structures will possibly enable unconventional means of studying complex endovascular intervention problems that are otherwise hard to address using existing models.

scholarly journals PapRIV, a BV-2 microglial cell activating quorum sensing peptide

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yorick Janssens ◽  
Nathan Debunne ◽  
Anton De Spiegeleer ◽  
Evelien Wynendaele ◽  
Marta Planas ◽  
...  
Keyword(s):  
Quorum Sensing ◽  
Cell Model ◽  
Dependent Manner ◽  
Communication Signals ◽  
Gram Positive Bacteria ◽  
A Cell ◽  
Gastro Intestinal Tract

AbstractQuorum sensing peptides (QSPs) are bacterial peptides produced by Gram-positive bacteria to communicate with their peers in a cell-density dependent manner. These peptides do not only act as interbacterial communication signals, but can also have effects on the host. Compelling evidence demonstrates the presence of a gut-brain axis and more specifically, the role of the gut microbiota in microglial functioning. The aim of this study is to investigate microglial activating properties of a selected QSP (PapRIV) which is produced by Bacillus cereus species. PapRIV showed in vitro activating properties of BV-2 microglia cells and was able to cross the in vitro Caco-2 cell model and reach the brain. In vivo peptide presence was also demonstrated in mouse plasma. The peptide caused induction of IL-6, TNFα and ROS expression and increased the fraction of ameboid BV-2 microglia cells in an NF-κB dependent manner. Different metabolites were identified in serum, of which the main metabolite still remained active. PapRIV is thus able to cross the gastro-intestinal tract and the blood–brain barrier and shows in vitro activating properties in BV-2 microglia cells, hereby indicating a potential role of this quorum sensing peptide in gut-brain interaction.

scholarly journals The Role of Biomimetic Hypoxia on Cancer Cell Behaviour in 3D Models: A Systematic Review

Cancers ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1334
Author(s):  
Ye Liu ◽  
Zahra Mohri ◽  
Wissal Alsheikh ◽  
Umber Cheema
Keyword(s):  
Systematic Review ◽  
Cellular Response ◽  
3D Culture ◽  
3D Models ◽  
In Vitro Models ◽  
Research Findings ◽  
Tissue Models

The development of biomimetic, human tissue models is recognized as being an important step for transitioning in vitro research findings to the native in vivo response. Oftentimes, 2D models lack the necessary complexity to truly recapitulate cellular responses. The introduction of physiological features into 3D models informs us of how each component feature alters specific cellular response. We conducted a systematic review of research papers where the focus was the introduction of key biomimetic features into in vitro models of cancer, including 3D culture and hypoxia. We analysed outcomes from these and compiled our findings into distinct groupings to ascertain which biomimetic parameters correlated with specific responses. We found a number of biomimetic features which primed cancer cells to respond in a manner which matched in vivo response.

Modulation of vascular tone in renal microcirculation by erythrocytes: role of EDRF

1993 ◽  
Vol 264 (1) ◽  
pp. H190-H195 ◽  
Author(s):  
J. D. Imig ◽  
D. Gebremedhin ◽  
D. R. Harder ◽  
R. J. Roman
Keyword(s):  
Vascular Tone ◽  
Physiological Salt Solution ◽  
Nitric Oxide Synthase Inhibitor ◽  
Renal Microcirculation ◽  
Vasoconstrictor Response ◽  
A Cell ◽  
Afferent Arterioles ◽  
Synthase Inhibitor

The effect of erythrocytes (red blood cells, RBC) on vascular tone in the renal microcirculation was examined using the juxtamedullary nephron microvascular preparation perfused in vitro with a physiological salt solution containing 5% albumin. The basal diameters of the arcuate, interlobular, proximal, and distal afferent arterioles averaged 444 +/- 24, 74 +/- 3, 29 +/- 1, and 19 +/- 1 micron, respectively, when perfused with a cell-free solution at a pressure of 80 mmHg. The diameters of the arcuate and interlobular arteries increased by 14 +/- 4 and 13 +/- 4%, respectively, whereas the diameter of the proximal and distal portions of the afferent arterioles decreased by 7 +/- 2% when perfusion pressure was elevated from 80 to 160 mmHg. The addition of RBC to the perfusate reduced the basal diameters of interlobular and afferent arterioles by 11 +/- 4 and 15 +/- 3%, respectively. The maximal vasoconstrictor response was seen after the addition of only 1% RBC to the perfusate. Removal of platelets did not block the vasoconstrictor response to addition of RBC to the perfusate. The role of endothelium-derived relaxing factor (EDRF) in the vasoconstrictor response to RBC was studied by addition of nitric oxide synthase inhibitor, N omega-nitro-L-arginine (L-NNA, 100 microM) to the perfusate. L-NNA reduced the basal diameters of interlobular and afferent arterioles by 7 +/- 3 and 9 +/- 3%, respectively, and abolished the vasoconstrictor response to RBC. L-NNA had no effect on the pressure-diameter relationships of the preglomerular vasculature when added to perfusates already containing RBC.(ABSTRACT TRUNCATED AT 250 WORDS)

The recombinant lectin-like domain of thrombomodulin inhibits angiogenesis through interaction with Lewis Y antigen

Blood ◽  
2012 ◽  
Vol 119 (5) ◽  
pp. 1302-1313 ◽  
Author(s):  
Cheng-Hsiang Kuo ◽  
Po-Ku Chen ◽  
Bi-Ing Chang ◽  
Meng-Chen Sung ◽  
Chung-Sheng Shi ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Egf Receptor ◽  
Tube Formation ◽  
Endothelial Tube Formation ◽  
A Cell ◽  
Lewis Y ◽  
Tm Domain

AbstractLewis Y Ag (LeY) is a cell-surface tetrasaccharide that participates in angiogenesis. Recently, we demonstrated that LeY is a specific ligand of the recombinant lectin-like domain of thrombomodulin (TM). However, the biologic function of interaction between LeY and TM in endothelial cells has never been investigated. Therefore, the role of LeY in tube formation and the role of the recombinant lectin-like domain of TM—TM domain 1 (rTMD1)—in antiangiogenesis were investigated. The recombinant TM ectodomain exhibited lower angiogenic activity than did the recombinant TM domains 2 and 3. rTMD1 interacted with soluble LeY and membrane-bound LeY and inhibited soluble LeY-mediated chemotaxis of endothelial cells. LeY was highly expressed on membrane ruffles and protrusions during tube formation on Matrigel. Blockade of LeY with rTMD1 or Ab against LeY inhibited endothelial tube formation in vitro. Epidermal growth factor (EGF) receptor in HUVECs was LeY modified. rTMD1 inhibited EGF receptor signaling, chemotaxis, and tube formation in vitro, and EGF-mediated angiogenesis and tumor angiogenesis in vivo. We concluded that LeY is involved in vascular endothelial tube formation and rTMD1 inhibits angiogenesis via interaction with LeY. Administration of rTMD1 or recombinant adeno-associated virus vector carrying TMD1 could be a promising antiangiogenesis strategy.

The Use of Erythropoietin in the Treatment of Post-bone Marrow Transplatation Anemia

1993 ◽  
Vol 16 (5_suppl) ◽  
pp. 8-12 ◽  
Author(s):  
A.M. Vannucchi ◽  
A. Bosi ◽  
A. Grossi ◽  
S. Guidi ◽  
R. Saccardi ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Clinical Trials ◽  
Bone Marrow Transplantation ◽  
Blood Transfusion ◽  
In Vitro Models ◽  
Immunosuppressive Drug ◽  
Number Of Patients

The issue of the role of erythropoietin (Epo) in the erythroid reconstitution after bone marrow transplantation (BMT) has been addressed in several recent studies. A defective Epo production in response to anemia has been shown to occur in patients undergoing allogeneic BMT unlike in most of those subjected to an autologous rescue. The factors involved in the inadeguate Epo production in BMT are discussed, with particular attention to the role of the immunosuppressive drug cyclosporin-A, which has been shown to inhibit Epo production in both in vivo and in vitro models. The observation of defective Epo production eventually led to the development of clinical trials of recombinant human Epo (rhEpo) administration in BMT patients; the aims of these studies were to stimulate erythroid engraftment, hence reducing blood transfusion exposure. Although the number of patients studied up to now is relatively small, a benefit from rhEpo administration in terms of accelerated erythroid engraftment seems very likely, and it may also be associated with decreased transfusional needs in most treated patients. However, further studies are needed to better define indications, dosages and schedules of rhEpo in BMT patients.

scholarly journals Tendon Extracellular Matrix Remodeling and Defective Cell Polarization in the Presence of Collagen VI Mutations

Cells ◽  
2020 ◽  
Vol 9 (2) ◽  
pp. 409 ◽  
Author(s):  
Manuela Antoniel ◽  
Francesco Traina ◽  
Luciano Merlini ◽  
Davide Andrenacci ◽  
Domenico Tigani ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Critical Role ◽  
Active Form ◽  
Congenital Muscular Dystrophy ◽  
Cell Polarization ◽  
Pcr Analysis ◽  
Matrix Remodeling ◽  
Collagen Vi

Mutations in collagen VI genes cause two major clinical myopathies, Bethlem myopathy (BM) and Ullrich congenital muscular dystrophy (UCMD), and the rarer myosclerosis myopathy. In addition to congenital muscle weakness, patients affected by collagen VI-related myopathies show axial and proximal joint contractures, and distal joint hypermobility, which suggest the involvement of tendon function. To gain further insight into the role of collagen VI in human tendon structure and function, we performed ultrastructural, biochemical, and RT-PCR analysis on tendon biopsies and on cell cultures derived from two patients affected with BM and UCMD. In vitro studies revealed striking alterations in the collagen VI network, associated with disruption of the collagen VI-NG2 (Collagen VI-neural/glial antigen 2) axis and defects in cell polarization and migration. The organization of extracellular matrix (ECM) components, as regards collagens I and XII, was also affected, along with an increase in the active form of metalloproteinase 2 (MMP2). In agreement with the in vitro alterations, tendon biopsies from collagen VI-related myopathy patients displayed striking changes in collagen fibril morphology and cell death. These data point to a critical role of collagen VI in tendon matrix organization and cell behavior. The remodeling of the tendon matrix may contribute to the muscle dysfunction observed in BM and UCMD patients.

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