Abstract P031: Enhanced Cardiac Progenitor Cell Function and Differentiation in a Naturally Derived Extracellular Matrix

2011 ◽  
Vol 109 (suppl_1) ◽  
Author(s):  
Kristin M French ◽  
Jessica A DeQuach ◽  
Karen L Christman ◽  
Michael E Davis
Keyword(s):  
Extracellular Matrix ◽  
Smooth Muscle ◽  
Progenitor Cells ◽  
Troponin I ◽  
Cell Function ◽  
Cultured Cells ◽  
Current Treatment ◽  
Gene Expressions ◽  
Antioxidant Genes ◽  
Functional Studies

Cardiovascular disease, including myocardial infarction, is a leading cause of death worldwide. Though several pharmacological treatments for severe dysfunction exist, much recent work has focused on the transplantation of adult-derived stem and progenitor cells. Early acute functional improvements have been noted, however long-term clinical efficacy is hampered by poor cell survival and engraftment. While the current treatment is infusion into the coronary artery, biomaterials may play an important role in modulating implanted cell function. This work aims to establish the role that a naturally derived extracellular matrix plays in the differentiation of cardiac progenitor cells (CPCs) and their potentially protective enzymatic systems. To test this hypothesis, we cultured rat CPCs in a naturally derived porcine ECM (pECM) and compared it to Collagen I. Quantitative real-time PCR was used to assess expression of cardiac, endothelial and smooth muscle markers. Additionally, angiotensin receptor (AT1R and AT2R) and antioxidant gene expressions were evaluated to determine the protective qualities of pECM. Preliminary data at 2 days following LIF removal demonstrate an increase in the expression of cardiac lineage markers (Nkx-2.5, Gata-4, α-MHC, and troponin I) in pECM compared to collagen. Smooth muscle markers, smooth muscle α-actin and sm22α as well as the endothelial marker Flk1 were also increased in pECM samples. Increased expression was also seen for antioxidant genes GPX1, SOD1, SOD2 and catalase in pECM cultured cells. Culturing in pECM for 7 days demonstrated an increase in Flt-1 and α-myosin heavy chain, indicating a potential increase in cardiogenesis. Moreover a 60% reduction in AT1R gene expression was observed with no significant change in AT2R expression. Our data demonstrate that culturing CPCs in naturally derived matrices may provide protection and enhance differentiation compared to collagen (present in high amounts in scarred myocardium). Future work will further elucidate this protective effect of AT1R downregulation and antioxidant increases in functional studies. In conclusion, pECM may be a potential cell delivery scaffold in post-MI treatment given its protective nature and improved differentiation influence.

scholarly journals Changes in the components of extracellular matrix and in growth properties of cultured aortic smooth muscle cells upon ascorbate feeding.

1982 ◽  
Vol 92 (2) ◽  
pp. 462-470 ◽  
Author(s):  
E Schwartz ◽  
R S Bienkowski ◽  
B Coltoff-Schiller ◽  
S Goldfischer ◽  
O O Blumenfeld
Keyword(s):  
Extracellular Matrix ◽  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Time Course ◽  
Cultured Cells ◽  
Growth Parameters ◽  
Muscle Cells ◽  
Cellular Protein ◽  
Collagen Accumulation ◽  
The Matrix

Culture conditions can modify the composition of the extracellular matrix of cultured calf aortas smooth muscle cells. In the absence of ascorbate the major components of the matrix are microfibrillar proteins; deposition of collagen occurs upon ascorbate supplementation and, with increased time of exposure of cells to ascorbate, collagen becomes the dominant protein of the extracellular matrix (greater than 80%). Collagen accumulation follows a sigmoidal time-course, suggesting that it is a cooperative phenomenon. Covalent crosslinks are not required for collagen accumulation in the matrix. Microfibrillar proteins and increased amounts of proteoglycans and fibronectin accumulate concurrently with collagen but elastin deposition was not observed either with or without ascorbate feeding. Addition of ascorbate leads to a general stimulation of incorporation of [14C]proline into cellular protein and to changes in cell growth parameters and morphology: cell-doubling time decreases from 62 to 47 h and plating efficiency increases approximately fourfold. We conclude that the composition of the extracellular matrix assembled by cultured cells is subject to experimental manipulation and that changes in endogenously deposited matrix may have significant effects on cellular functions.

Context-Dependent Regulation of Nrf2/ARE Axis on Vascular Cell Function during Hyperglycemic Condition

2020 ◽  
Vol 16 (8) ◽  
pp. 797-806 ◽  
Author(s):  
Tharmarajan Ramprasath ◽  
Allen John Freddy ◽  
Ganesan Velmurugan ◽  
Dhanendra Tomar ◽  
Balakrishnan Rekha ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
High Glucose ◽  
Molecular Mechanisms ◽  
Cell Function ◽  
Vascular Dysfunction ◽  
Redox Balance ◽  
Antioxidant Response ◽  
Antioxidant Genes ◽  
Increased Risk ◽  
Context Dependent

: Diabetes mellitus is associated with an increased risk of micro and macrovascular complications. During hyperglycemic conditions, endothelial cells and vascular smooth muscle cells are exquisitely sensitive to high glucose. This high glucose-induced sustained reactive oxygen species production leads to redox imbalance, which is associated with endothelial dysfunction and vascular wall remodeling. Nrf2, a redox-regulated transcription factor plays a key role in the antioxidant response element (ARE)-mediated expression of antioxidant genes. Although accumulating data indicate the molecular mechanisms underpinning the Nrf2 regulated redox balance, understanding the influence of the Nrf2/ARE axis during hyperglycemic condition on vascular cells is paramount. This review focuses on the context-dependent role of Nrf2/ARE signaling on vascular endothelial and smooth muscle cell function during hyperglycemic conditions. This review also highlights improving the Nrf2 system in vascular tissues, which could be a potential therapeutic strategy for vascular dysfunction.

Abstract 1162: Proteomic Characterization of the Secretome of Peripheral Blood-derived Smooth Muscle Progenitors

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
David Simper ◽  
Ursula Mayr ◽  
Ulrike Benbow ◽  
Andrew Newby ◽  
Qingbo Xu ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Smooth Muscle ◽  
Progenitor Cells ◽  
Conditioned Medium ◽  
Inflammatory Cytokines ◽  
Two Dimensional Gel Electrophoresis ◽  
Paracrine Factors ◽  
Myeloid Lineage ◽  
Matrix Deposition ◽  
Proteomic Approach

Background. Recent studies on circulating progenitor cells of the myeloid lineage have led to a new appreciation of their secretome, as paracrine factors may support tissue regeneration. Methods and Results. Using a mass-spectrometry-based proteomic approach complemented by protein separation using two-dimensional gel electrophoresis, we compared the conditioned medium of plasma-derived smooth muscle progenitors (SPCs) and human aortic smooth muscle cells (SMCs). In total, over 150 individual protein features were identified. The majority of proteins were common to both cell lines, but higher amounts of the interstitial collagenase MMP-1, and of inflammatory cytokines, i.e. IL-8 and MCP-1, were found in the conditioned medium of SMCs compared to SPCs, which was subsequently verified by multiplex cytokine assays. ELISA measurements also confirmed that the concentrations of MMP-1 in the conditioned medium of SMCs exceeded the levels in the supernatant of SPCs. Although MMP-1 activity was partially antagonized in SMCs by a coordinated increase in TIMP-1, MMP-1 activity remained lower in SPCs. As a functional consequence, SMCs shedded more N-cadherin, an established MMP target, from their cell surface and showed a stronger invasive capacity. In contrast, SPCs produced more collagen, fibronectin and biglycan, but less perlecan than SMCs. A proteomic comparison between SPCs and endothelial progenitor cells (EPCs) revealed that the production of extracellular matrix proteins and the attenuated secretion of inflammatory cytokines was a specific characteristic of SPCs. EPCs secreted high levels of cathepsins, predominantly cathepsin D, B, Z and L, which were not detected in the conditioned medium of SPCs. Conclusion. The present study constitutes the first comprehensive assessment of different circulating progenitors of the myeloid lineage demonstrating that apart from their potential physical contribution to lesion formation, SPCs might contribute to plaque stability by limiting inflammatory reactions and contributing to extracellular matrix deposition.

scholarly journals The Role of miRNAs in Extracellular Matrix Repair and Chronic Fibrotic Lung Diseases

Cells ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1706
Author(s):  
Kauna Usman ◽  
Aileen Hsieh ◽  
Tillie-Louise Hackett
Keyword(s):  
Extracellular Matrix ◽  
Pulmonary Disease ◽  
Lung Diseases ◽  
Cell Function ◽  
Mechanical Stability ◽  
Current Knowledge ◽  
Chronic Obstructive ◽  
Elastic Recoil ◽  
Gene Expressions ◽  
Chronic Lung Diseases

The lung extracellular matrix (ECM) plays a key role in the normal architecture of the lung, from embryonic lung development to mechanical stability and elastic recoil of the breathing adult lung. The lung ECM can modulate the biophysical environment of cells through ECM stiffness, porosity, topography and insolubility. In a reciprocal interaction, lung ECM dynamics result from the synthesis, degradation and organization of ECM components by the surrounding structural and immune cells. Repeated lung injury and repair can trigger a vicious cycle of aberrant ECM protein deposition, accompanied by elevated ECM stiffness, which has a lasting effect on cell and tissue function. The processes governing the resolution of injury repair are regulated by several pathways; however, in chronic lung diseases such as asthma, chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary disease (IPF) these processes are compromised, resulting in impaired cell function and ECM remodeling. Current estimates show that more than 60% of the human coding transcripts are regulated by miRNAs. miRNAs are small non-coding RNAs that regulate gene expressions and modulate cellular functions. This review is focused on the current knowledge of miRNAs in regulating ECM synthesis, degradation and topography by cells and their dysregulation in asthma, COPD and IPF.

ADHESION OF BLOOD PLATELETS TO THE EXTRACELLULAR MATRIX OF CULTURED CELLS IN WHICH COLLAGEN SYNTHESIS IS IMPAIRED OR INDUCED

1987 ◽  
Author(s):  
G A Hindriks ◽  
H C de Boer ◽  
H K Nieuwenhuis ◽  
J J Sixma ◽  
P H G de Groot
Keyword(s):  
Extracellular Matrix ◽  
Endothelial Cells ◽  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Collagen Synthesis ◽  
Platelet Adhesion ◽  
Cultured Cells ◽  
Type I ◽  
Shear Rates ◽  
Adhesion Of Platelets

One of the first phenomena in the hemostatic plug formation is adhesion of platelets to the subendothelium or to the perivascular connective tissue. With a rectangular perfusion chamber (Sakariassen et al., J.Lab.Clin.Med.(1983) 102, 522-535) it is possible to study platelet adhesion in flowing blood to extracellular matrix (ECM) of cultured cells.Collegen type I and III play an important role in the adhesion of platelets. To study their role in more detail, cultured cells with changed collagen synthesis were used. For this purpose, we used fibroblasts of a patient with Osteogenesis Imperfecta type I (0.I.)(characterized by impaired collagen synthesis) cultured from a skin biopsy and used in the fourth passage. Platelet adhesion to ECM of 0.1. fibroblasts was decreased in comparison to ECM of normal fibroblasts (8% versus 17% at low shear rates (300 s™1 ) and 5% versus 24% at high shear rates (1300 s™1 ) after perfusion with whole blood for 5 min). No aggregate formation occurred on patient’s matrices, whereas small aggregates were observed on ECM of normal fibroblasts. Addition of ascorbic acid to culture medium of fibroblasts, smooth muscle cells and endothelial cells causes increased collagen synthesis with increased fibril formation. Platelet adhesion to ECM of endothelial cells showed an increased adhesion of 25% only at high wall shear rates (1300 s™1 ). Induction of collagen synthesis in smooth muscle cells resulted in a strong increase of thrombus formation on their matrices. These data indicate that platelet adhesion to the matrix of cultured cells is strongly dependent on the quantity and nature of the reactive collagens.

scholarly journals Human embryonic stem cell−derived vascular progenitor cells capable of endothelial and smooth muscle cell function

2010 ◽  
Vol 38 (3) ◽  
pp. 246-257.e1 ◽  
Author(s):  
Katherine L. Hill ◽  
Petra Obrtlikova ◽  
Diego F. Alvarez ◽  
Judy A. King ◽  
Susan A. Keirstead ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Stem Cell ◽  
Embryonic Stem Cell ◽  
Smooth Muscle Cell ◽  
Progenitor Cells ◽  
Muscle Cell ◽  
Human Embryonic Stem Cell ◽  
Cell Function ◽  
Embryonic Stem ◽  
Vascular Progenitor Cells
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