Biomedical subjects

Amy P Wong

Publications and source records attributed to Amy P Wong.

7 recordsLinked to original sources

PubMed2006

Cell-based tissue engineering for lung regeneration.

Emphysema is a chronic lung disease characterized by alveolar enlargement and tissue loss. Tissue engineering represents an attractive potential for regeneration of several organ systems. The complex three-dimensional architectural structure of lung parenchyma requiring connections of alveolar units to airways and the pulmonary circulation makes this strategy less optimistic. In the present study, we used Gelfoam sponge as a scaffold material, supplemented with fetal rat lung cells as progenitors, to explore the potential application of cell-based tissue engineering for lung regeneration in adult rats. After injection into lung parenchyma, the sponge showed porous structures similar to alveolar units. It did not induce severe local inflammatory response. Fetal lung cells in the sponge were able to survive in the adult lung for at least 35 days, determined by CMTMR [5-(and-6)-{[(4-chloromethyl)benzoyl]amino}tetramethylrhodamine] labeling. Proliferation of cells within the sponge was demonstrated in vivo by bromodeoxyuridine (BrdU) labeling. Cells formed "alveolar-like structures" at the border between the sponge and the surrounding lung tissue with positive immunohistochemical staining for epithelial and endothelial cells. Neovascularization of the sponge was demonstrated with India ink perfusion. The sponge degraded after several months. This study suggests that cell-based tissue engineering possesses the potential to regenerate alveolar-like structures, an important step towards our ultimate goal of lung regeneration.

Absorbable Implants↗

PubMed2006

Altered expression of disintegrin metalloproteinases and their inhibitor in human dilated cardiomyopathy.

BACKGROUND: Disintegrin metalloproteinases (ADAMs) may contribute to structural cardiac remodeling by altering cell-surface matrix receptors (integrins) and activating potent biomolecules. We compared expression of ADAMs, their endogenous inhibitor tissue inhibitor of metalloproteinases (TIMP)-3, and integrins in human heart tissue with varied patterns of structural remodeling. METHODS AND RESULTS: Myocardium was obtained from patients with dilated cardiomyopathy (n=20), hypertrophic obstructive cardiomyopathy (n=5), and nonfailing donor hearts (n=7). Paired samples (n=10) were obtained before left ventricular assist device insertion and at transplantation. The expressions of ADAM10, ADAM12, ADAM15, and ADAM17, TIMP-3, and integrin receptors beta1D and beta3 were determined by quantitative immunoblotting. Integrin shedding was assessed by the ratio of integrin cleavage products to intact protein abundance. Confocal microscopy was performed. Dilated cardiomyopathy was characterized by increased ADAM10 and ADAM15 expression and reduced TIMP-3 expression. The integrin beta1D cleavage ratio was elevated, indicating receptor shedding. ADAM10 and ADAM15 expressions correlated with the cleavage ratio. ADAM10 colocalized with integrin beta1D by confocal microscopy. ADAM10 expression correlated with clinical indices of chamber dilatation and systolic dysfunction. Hemodynamic unloading reduced ADAM10 and ADAM12 expressions and increased integrin beta1D expression. ADAM12 and integrin beta1D expressions were increased in HOCM. ADAM17 was increased in both dilated cardiomyopathy and hypertrophic obstructive cardiomyopathy. CONCLUSIONS: Disintegrin metalloproteinases are differentially expressed in human myocardium, reflecting the underlying pattern of structural remodeling. ADAM10 and ADAM15 may contribute to cardiac dilatation by reducing cell-matrix interactions via integrin shedding. Targeting disintegrin metalloproteinases, perhaps by restoring deficient TIMP-3 levels with gene or cell-based therapies, may prevent progressive chamber dilatation in human dilated cardiomyopathy.

ADAM Proteins↗

PubMed2005

In vitro differences between venous and arterial-derived smooth muscle cells: potential modulatory role of decorin.

OBJECTIVE: We analyzed the phenotypic and functional differences between venous and arterial smooth muscle cells (SMC) and the role of decorin in modulating these differences. METHODS AND RESULTS: SMC were isolated from the jugular veins and carotid arteries of male white New Zealand rabbits. Venous SMC demonstrated increased proliferation (2-fold, p<0.001), migration (1.7-fold, p<0.001), and collagen synthesis (4-fold, p<0.001), with decreased adhesion to collagen and fibronectin (1.2-fold, p<0.01) compared to arterial SMC. Higher levels of gelatinase activity (MMP-2 and MMP-9) and tissue inhibitor of metalloproteinase (TIMP) were also observed in venous SMC. Venous SMC demonstrated increased expression of SMemb and decreased expression of SM1--markers of a dedifferentiated and differentiated phenotype, respectively. Arterial SMC produced increased levels of the inhibitory proteoglycan, decorin, compared to venous SMC. Conditioned medium from arterial SMC (ASMC-CM) significantly decreased DNA synthesis, collagen synthesis, and gelatinase activity in venous SMC. Removal of decorin from ASMC-CM by immunoprecipitation significantly reversed the inhibitory effects of ASMC-CM on venous SMC proliferation and collagen synthesis but did not affect gelatinase activities. CONCLUSION: Venous SMC are more dedifferentiated and demonstrate increased proliferative and synthetic capacity than arterial SMC. Differential decorin expression between arterial and venous SMC contributes to these differences in biologic behavior. Venous SMC properties may contribute to accelerated atherosclerosis in venous bypass grafts.

Animals↗

PubMed2005

Directing cell migration with asymmetric micropatterns.

This report shows that the direction of polarization of attached mammalian cells determines the direction in which they move. Surfaces micropatterned with appropriately functionalized self-assembled monolayers constrain individual cells to asymmetric geometries (for example, a teardrop); these geometries polarize the morphology of the cell. After electrochemical desorption of the self-assembled monolayers removes these constraints and allows the cells to move across the surface, they move toward their blunt ends.

Animals↗

PubMed2004

Selective deposition of native cell membranes on biocompatible micropatterns.

We establish two methods to deposit native biomembranes (human erythrocyte membranes and sarcoplasmic reticulum membranes) selectively onto biocompatible microtemplates. The first method utilizes UV photolithography to micropattern the regenerated cellulose, while the second uses the "stamping" of protein barriers onto homogeneous cellulose supports. The relatively simple methods established here allow for the position selective spreading of three-dimensional native cells into two-dimensional films, retaining the orientation and lateral density of transmembrane proteins in their native state.

Biocompatible Materials↗

PubMed2003

Effects of intravascular cryotherapy on vessel wall repair in a balloon-injured rabbit iliac artery model.

OBJECTIVE: Although the application of cold energy, cryotherapy, has been shown to cause selective damage to cellular components with preservation of matrix structure resulting in less fibrosis in a variety of tissues, the effects of intravascular cryotherapy on vessel wall repair after balloon angioplasty are unknown. We sought to characterize the effects of cryotherapy application on vessel wall repair after balloon angioplasty and study the relationship between collagen accumulation in the vessel wall and late lumen loss as assessed by serial intravascular ultrasound. METHODS: The immediate, early (72 h) and late (10 weeks) effects of three intravascular cryotherapy application time periods (60, 120 and 240 s) after iliac artery balloon angioplasty ('cryotherapy') were compared with balloon angioplasty alone ('control') in 59 rabbits. Arterial lumen area was measured by intravascular ultrasound immediately after the procedure, at 72 h and at 10 weeks. Collagen content was calculated separately for intima and media/adventitia layers and correlated with late lumen loss. RESULTS: Cryotherapy produced average vessel wall temperature of -26 degrees C (range, -20 to -45 degrees C) and resulted in significantly larger lumen cross-sectional area (CSA) immediately after application (5.74+/-1.18 vs. 4.14+/-0.75 mm(2), P=0.008) but was not different than control arteries at 10 weeks. At 72 h, there was extensive cell loss in the medial and adventitial layers accompanied by increased macrophage infiltration in cryotherapy treated arteries compared to control. At 10 weeks, intimal hyperplasia was increased 2-fold in cryotherapy treated arteries. Collagen content was increased 2-fold in the medial/adventitial layers, and nearly 3-fold in the intima of cryotherapy treated arteries. Collagen content in arterial intima (P=0.01) as well as media/adventitia (P=0.005) positively correlated with late lumen loss. Foci of chondro- and osseous metaplasia and calcification were evident at the medial-adventitial junction in cryotherapy treated arteries at 10 weeks. CONCLUSION: Intravascular cryotherapy induced early arterial wall cell loss and late intimal hyperplasia, vascular fibrosis and chondro- and osseous metaplastic changes with no late beneficial effects on lumen area compared to balloon angioplasty alone. Collagen accumulation in all three layers of the vessel wall contributes to the development of late inward remodeling after balloon angioplasty.

Animals↗

PubMed2002

Molecular topography imaging by intermembrane fluorescence resonance energy transfer.

Fluorescence resonance energy transfer (FRET) between lipid-linked donor and acceptor molecules in two apposing lipid bilayer membranes is used to resolve topographical features at an intermembrane junction. Efficient energy transfer occurs when the membranes are apposed closely, which creates an image, or footprint, that maps the contact zone and reveals nanometer-scale topographical structures. We experimentally characterize intermembrane FRET by using a supported membrane junction consisting of a glass-supported lipid membrane, onto which a second membrane is deposited by rupture of a giant vesicle. A series of membrane junctions containing different glycolipids (phosphatidylinositol and ganglioside G(M1)), protein (cholera toxin), and lipid-linked polyethylene glycol are studied. The carbohydrate and protein components influence the intermembrane separation. Differential FRET efficiency is clearly distinguishable for each case. Quantitative analysis of the FRET efficiency yields measurements of intermembrane-separation distances that agree precisely with structural data on G(M1) and cholera toxin. The lateral arrangement of molecular species on the membrane surface thus can be discerned by their influence on membrane spacing without the need for direct labeling of the molecule of interest. In the case of polyethylene glycol lipid-containing membrane junctions, imaging by intermembrane FRET reveals spontaneously forming patterns that are not visible in conventional fluorescence images.

Cholera Toxin↗