Fibrin Gel Model for Assessment of Cellular Contractility

2009 ◽  
pp. 251-259 ◽  
Author(s):  
Sharona Even-Ram
Keyword(s):  
Fibrin Gel

The Enhancement Effect of Acetylcholine and Pyridostigmine on Bone-Tendon Interface Healing in a Murine Rotator Cuff Model

2021 ◽  
pp. 036354652098868
Author(s):  
Zhanwen Wang ◽  
Yang Chen ◽  
Han Xiao ◽  
Shengcan Li ◽  
Tao Zhang ◽  
...  
Keyword(s):  
Rotator Cuff ◽  
Rotator Cuff Repair ◽  
Early Stage ◽  
Drug Carrier ◽  
Acetylcholinesterase Inhibitor ◽  
Healing Process ◽  
Enhancement Effect ◽  
M2 Macrophages ◽  
Fibrin Gel ◽  
Cuff Repair

Background: How to improve rotator cuff healing remains a challenge. Little is known about the effect of the parasympathetic transmitter acetylcholine (ACh) and the acetylcholinesterase inhibitor pyridostigmine (PYR), both of which have anti-inflammatory properties, in the healing process of rotator cuff injury. Hypothesis: ACh and PYR could enhance bone-tendon interface healing in a murine model of rotator cuff repair. Study Design: Controlled laboratory study. Methods: A total of 160 C57BL/6 mice underwent unilateral rotator cuff repair surgery. Fibrin gel (FG) was used as a drug carrier. The mice were randomly assigned to 4 groups with 40 mice per group: FG group (received FG alone), 10-5 M ACh group (received FG containing 10-5 M ACh), 10-6 M ACh group (received FG containing 10-6 M ACh), and PYR group (received FG containing 25 µg of PYR). Ten mice in each group were euthanized at 2, 4, 8, and 12 weeks postoperatively. Histologic, immunohistochemical, and biomechanical evaluations were performed for analysis. Results: Histologically, fibrocartilage-like tissue was shown at the repaired site. The proteoglycan content of the 10-5 M ACh group was significantly increased compared with the FG group at 4 weeks. M2 macrophages were identified at the repaired site for all groups at 2 and 4 weeks. At 8 weeks, M2 macrophages withdrew back to the tendon in the FG group, but a number of M2 macrophages were retained at the repaired sites in the ACh and PYR groups. Biomechanically, failure load and stiffness of the ACh and PYR groups were significantly higher than those of the FG group at 4 weeks. The stiffness of the ACh and PYR groups was significantly increased compared with the FG group at 8 weeks ( P < .001 for all). At 12 weeks, most of the healing properties of the ACh and PYR groups were not significantly different compared with the FG group. Conclusion: ACh and PYR enhanced the early stage of bone-tendon insertion healing after rotator cuff repair. Clinical Relevance: These findings imply that ACh and PYR could serve as potential therapeutic strategies for rotator cuff healing.

scholarly journals CD90+CD146+ identifies a pulmonary mesenchymal cell subtype with both immune modulatory and perivascular-like function in postnatal human lung

2020 ◽  
Vol 318 (4) ◽  
pp. L813-L830 ◽  
Author(s):  
Limei Wang ◽  
Patrick Dorn ◽  
Soheila Zeinali ◽  
Laurène Froment ◽  
Sabina Berezowska ◽  
...  
Keyword(s):  
Self Assembly ◽  
Human Lung ◽  
Elective Surgery ◽  
Growth Factor Receptor ◽  
Mesenchymal Cell ◽  
Confocal Imaging ◽  
Chronic Obstructive ◽  
Fibrin Gel ◽  
Lung Lesions ◽  
Chip Technology

Our understanding of mesenchymal cell subsets and their function in human lung affected by aging and in certain disease settings remains poorly described. We use a combination of flow cytometry, prospective cell-sorting strategies, confocal imaging, and modeling of microvessel formation using advanced microfluidic chip technology to characterize mesenchymal cell subtypes in human postnatal and adult lung. Tissue was obtained from patients undergoing elective surgery for congenital pulmonary airway malformations (CPAM) and other airway abnormalities including chronic obstructive pulmonary disease (COPD). In microscopically normal postnatal human lung, there was a fivefold higher mesenchymal compared with epithelial (EpCAM+) fraction, which diminished with age. The mesenchymal fraction composed of CD90+ and CD90+CD73+ cells was enriched in CXCL12 and platelet-derived growth factor receptor-α (PDGFRα) and located in close proximity to EpCAM+ cells in the alveolar region. Surprisingly, alveolar organoids generated from EpCAM+ cells supported by CD90+ subset were immature and displayed dysplastic features. In congenital lung lesions, cystic air spaces and dysplastic alveolar regions were marked with an underlying thick interstitium composed of CD90+ and CD90+PDGFRα+ cells. In postnatal lung, a subset of CD90+ cells coexpresses the pericyte marker CD146 and supports self-assembly of perfusable microvessels. CD90+CD146+ cells from COPD patients fail to support microvessel formation due to fibrinolysis. Targeting the plasmin-plasminogen system during microvessel self-assembly prevented fibrin gel degradation, but microvessels were narrower and excessive contraction blocked perfusion. These data provide important new information regarding the immunophenotypic identity of key mesenchymal lineages and their change in a diverse setting of congenital lung lesions and COPD.

Notch restricts lymphatic vessel sprouting induced by vascular endothelial growth factor

Blood ◽  
2011 ◽  
Vol 118 (4) ◽  
pp. 1154-1162 ◽  
Author(s):  
Wei Zheng ◽  
Tuomas Tammela ◽  
Masahiro Yamamoto ◽  
Andrey Anisimov ◽  
Tanja Holopainen ◽  
...  
Keyword(s):  
Notch Signaling ◽  
Cell Fate ◽  
Target Genes ◽  
Notch Pathway ◽  
Lymphatic Vessels ◽  
Soluble Form ◽  
Fibrin Gel ◽  
3 Dimensional ◽  
Endothelial Growth Factor

Abstract Notch signaling plays a central role in cell-fate determination, and its role in lateral inhibition in angiogenic sprouting is well established. However, the role of Notch signaling in lymphangiogenesis, the growth of lymphatic vessels, is poorly understood. Here we demonstrate Notch pathway activity in lymphatic endothelial cells (LECs), as well as induction of delta-like ligand 4 (Dll4) and Notch target genes on stimulation with VEGF or VEGF-C. Suppression of Notch signaling by a soluble form of Dll4 (Dll4-Fc) synergized with VEGF in inducing LEC sprouting in 3-dimensional (3D) fibrin gel assays. Expression of Dll4-Fc in adult mouse ears promoted lymphangiogenesis, which was augmented by coexpressing VEGF. Lymphangiogenesis triggered by Notch inhibition was suppressed by a monoclonal VEGFR-2 Ab as well as soluble VEGF and VEGF-C/VEGF-D ligand traps. LECs transduced with Dll4 preferentially adopted the tip cell position over nontransduced cells in 3D sprouting assays, suggesting an analogous role for Dll4/Notch in lymphatic and blood vessel sprouting. These results indicate that the Notch pathway controls lymphatic endothelial quiescence, and explain why LECs are poorly responsive to VEGF compared with VEGF-C. Understanding the role of the Notch pathway in lymphangiogenesis provides further insight for the therapeutic manipulation of the lymphatic vessels.

scholarly journals Optimized Fibrin Gel Bead Assay for the Study of Angiogenesis

10.3791/186 ◽  
2007 ◽  
Author(s):  
Martin N. Nakatsu ◽  
Jaeger Davis ◽  
Christopher C.W. Hughes
Keyword(s):  
Fibrin Gel ◽  
Gel Bead

scholarly journals Effects of Matrix Metalloproteinases on the Performance of Platelet Fibrin Gel Spiked With Cardiac Stem Cells in Heart Repair

2016 ◽  
Vol 5 (6) ◽  
pp. 793-803 ◽  
Author(s):  
Deliang Shen ◽  
Junnan Tang ◽  
Michael Taylor Hensley ◽  
Taosheng Li ◽  
Thomas George Caranasos ◽  
...  
Keyword(s):  
Stem Cells ◽  
Matrix Metalloproteinases ◽  
Cardiac Stem Cells ◽  
Fibrin Gel ◽  
Heart Repair

Abstract 427: Tissue Inhibitor of Matrix Metalloproteinase-3 (TIMP3) Provides Beneficial Effects Post-MI by Promoting Angiogenesis

2016 ◽  
Vol 119 (suppl_1) ◽  
Author(s):  
Abhijit R Takawale ◽  
Pu Zhang ◽  
Ratnadeep Basu ◽  
Abul Azad ◽  
Maikel Farhan ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Left Ventricular ◽  
Tissue Inhibitor Of Metalloproteinase ◽  
Lv Function ◽  
Vascular Density ◽  
Tissue Inhibitor ◽  
Infarct Zone ◽  
Fibrin Gel ◽  
Beneficial Effects

Introduction: Myocardial infarction (MI) results in loss of cardiomyocytes, adverse extracellular matrix (ECM) remodelling, leading to left ventricular (LV) dilation and dysfunction. Tissue inhibitor of metalloproteinase (TIMPs) are MMP inhibitors, main regulators of ECM integrity. TIMPs can also regulate other aspects of myocardial remodeling such as hypertrophy, fibrosis and inflammation. TIMP3 levels are reduced in the peri-infarct zone within 24 hours post-MI in mice. Hypothesis: Replenishment of TIMP3 post-MI limit infarct expansion, and attenuate LV dilation and dysfunction. Methods: MI was induced in adult male wildtype (C57BL/6) mice by ligation of the left anterior descending artery. Adenoviral constructs expressing human TIMP3 (Ad- hTIMP3) or no-TIMP (Ad-Null, control) were injected in the peri-infarct zone (5.4x10 7 pfu, 5 injections/heart). Cardiac function was assessed by echocardiography. Cardiomyocyte density (WGA/DAPI staining), vascular density (Fluo-lectin injection, CD31 IHC), ECM composition (PSR staining) were assessed at 3 and 7 days post-MI. In vitro, angiogenic potency of TIMP3 (rTIMP3) was assessed using the 3D fibrin gel-based angiogenesis assay using primary human vascular (HUVECs) and coronary artery endothelial cells (HCAECs), and co-IP between TIMP3 and VEGFR2. Results: Ad-TIMP3 injections significantly improved LV function and reduced LV dilation as compared to Ad-Null group post-MI. Infarct size was markedly reduced with TIMP3 injections and more viable myocytes were preserved in the infarct zone at 1wk post-MI. Ad-TIMP3-MI group showed a higher density of endothelial cells and increased coronary density in the infarct and peri-infarct regions compared to the Ad-null group. This suggested that Ad-TIMP3 promotes angiogenesis in the infarcted myocardium. In vitro studies confirmed that rTIMP3 promoted angiogenesis/sprouting in human endothelial cells up to100ng/ml. However at higher concentrations (>1ug/ml), rTIMP3 exerted anti-angiogenic effects by binding to VEGFR2. This function of rTIMP3 appears to be through an MMP-inhibitory mechanism. Conclusion: The novel pro-angiogenic function of TIMP3 post-MI could provide additional beneficial effects in post-MI treatment.

Preparation and characterization of poly(ε-caprolactone) scaffolds modified with cell-loaded fibrin gel

2019 ◽  
Vol 125 ◽  
pp. 683-689 ◽  
Author(s):  
Elbay Malikmammadov ◽  
Tugba Endogan Tanir ◽  
Aysel Kiziltay ◽  
Nesrin Hasirci
Keyword(s):  
Fibrin Gel
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