Tissue Engineering Therapy for Cardiovascular Disease

Nugent, Helen M.; Edelman, Elazer R.

doi:10.1161/01.res.0000073844.41372.38

Cited by 154 publications

(150 citation statements)

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“…26 In attempts to address these issues, several laboratories have developed compliant polyurethane composites. [27][28][29] In the approach presented here, we focus on elastin, which forms a crosslinked network in the arterial wall 30 and which, along with collagen, imparts elasticity and resiliency to the M-MASMTGGQQMG-HHHHHHH-DDDDK(LD-YAVTGRGDSPASSKPIA((VPGIG) 2 VPGKG(VPGIG) 2 ) 4 VP) 3 [41][42][43] this sequence serves as a ligand for the α v β 3 and α 5 β 1 integrins. 44,45 aECM 2 is a negative control for aECM 1, in which the sequence of the RGD cellbinding domain has been scrambled.…”

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confidence: 99%

Comparative Cell Response to Artificial Extracellular Matrix Proteins Containing the RGD and CS5 Cell-Binding Domains

2004

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This study addresses endothelial cell adhesion and spreading on a family of artificial extracellular matrix (aECM) proteins designed for application in small-diameter vascular grafts. The aECM proteins contain domains derived from elastin and from fibronectin. aECM 1 contains the RGD sequence from the tenth type III domain of fibronectin; aECM 3 contains the fibronectin CS5 cell-binding domain. Negative control proteins aECM 2 and 4 are scrambled versions of aECM 1 and 3, respectively.Competitive peptide inhibition studies and comparisons of positive and negative control proteins confirm that adhesion of HUVECs to aECM proteins 1 and 3 is sequence specific. When subjected to a normal detachment force of 780 pN, 3-fold more HUVEC remained adherent to aECM 1 than to aECM 3. HUVEC also spread more rapidly on aECM 1 than on aECM 3. These results (i) indicate that cellular responses to aECM proteins can be modulated through choice of cell-binding domain, and (ii) recommend the RGD sequence for applications that require rapid endothelial cell spreading and matrix adhesion. IntroductionCardiovascular disease afflicts more than 61 million Americans 1 and causes 4 million deaths each year in Europe. 2 Severe atherosclerosis often requires surgical removal of the affected tissue and implantation of an autologous or synthetic vascular graft. The most widely used materials in synthetic vascular grafts are poly(ethylene terephthalate) (PET) and expanded poly(tetrafluoroethylene) (ePTFE); when used in small-diameter grafts, both materials are characterized by high failure rates due to thrombosis and intimal hyperplasia. [3][4][5] Autologous saphenous vein yields higher patency rates than synthetic materials, particularly when used to reconstruct the infrapopliteal artery, 6,7 but autologous vein is limited in supply and patients often suffer from coexisting disease that makes these vessels unsuitable as grafts. 5,8 A family of artificial proteins that exhibits some of the essential characteristics of the extracellular matrix has been developed for application in small-diameter vascular grafts. [9][10][11][12][13] Artificial matrices that incorporate functional protein domains have been produced for a variety of applications. [14][15][16][17] The artificial extracellular matrix (aECM) proteins in this study consist of domains derived from elastin and fibronectin ( contains a T7 tag, a heptahistidine tag, an enterokinase cleavage site, and elastin-like domains containing lysine residues for crosslinking. The RGD cell-binding domain is found in aECM 1, whereas the minimal recognition sequence in the RGD cell-binding domain has been scrambled in aECM 2 to provide a negative control. aECM 3 includes the CS5 cell-binding domain whereas aECM 4, the negative control, contains a scrambled version of the CS5 cell-binding domain.An important criterion in the design of aECM proteins is the tensile modulus; compliance mismatch between the graft and tissue has been strongly implicated in graft failure. It is believed that flow...

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Comparative Cell Response to Artificial Extracellular Matrix Proteins Containing the RGD and CS5 Cell-Binding Domains

2004

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“…When cardiomyocytes are lost ,regional contractile dysfunction occur , and necrotized cardiac cells in infarcted cardiac tissues are replaced by fibroblasts progressively leading to scar tissue formation [18].Thus stem cell transplantation could be one of the best available life regenerative therapy for patients who suffer MI [19].The pluripotent properties of MSCs makes them an attractive therapeutic approach. The percentage of bone marrow MSC in adult is very small, approximately 0.001%-0.01% of cells isolated by Ficoll (1.073 g/ml) density interface adhere to the bottom of the flask.…”

Section: Discussionmentioning

confidence: 99%

5-Azacytidine Promotes Differentiation of Bone Marrow Derived Mesenchymal Stem Cells into Troponin Positive Cardiomyocyte‑Like Cells in Vitro.

Ahmedy¹,

Fathy²,

Noreldin³

et al. 2017

IOSR JBB

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“…[131][132][133][134][135] Frederick Schoen from Harvard Medical School stressed that the engineering of tissue requires an understanding of the relationships of structure to function in normal and pathological tissues (including mechanisms of embryological development, and functional tissue biomechanics and other structure-function correlations) and the ability to control cell and tissue responses to injury, physical stimuli, and biomaterial surfaces.…”

Section: Heart Valve Tissue Engineering and Regeneration Researchmentioning

confidence: 99%