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Biomedical subjects

I Vlodavsky

Publications and source records attributed to I Vlodavsky.

At least 73 records · Page 4Linked to original sources
PubMed1995

The extracellular matrix produced by bovine corneal endothelial cells contains progelatinase A.

Progelatinase A is a matrix metalloproteinase involved in the turnover of extracellular matrix (ECM). We report that the ECM produced by bovine corneal endothelial (BCE) cells contains progelatinase A free of tissue inhibitor of metalloproteinase (TIMP2). The matrix-bound progelatinase A can be activated by APMA to generate a 62 kDa and a 45 kDa species with enzymatic activity and is inhibited by TIMP2. The bound progelatinase can be released after treatment of the ECM with gelatinase B. These studies suggest that the ECM can function as a reservoir for progelatinase A which may be readily available for cells in processes such as metastasis, angiogenesis, inflammation and wound healing.

Animals↗
PubMed1995

Phosphorothioate oligodeoxynucleotides bind to basic fibroblast growth factor, inhibit its binding to cell surface receptors, and remove it from low affinity binding sites on extracellular matrix.

We studied the interactions of phosphorothioate oligodeoxynucleotides and heparin-binding growth factors. By means of a gel mobility shift assay, we demonstrated that phosphodiester and phosphorothioate homopolymers bound to basic fibroblast growth factor (bFGF). Binding of a probe phosphodiester oligodeoxynucleotide could also be shown for other proteins of the FGF family, including acidic fibroblast growth factor (aFGF), Kaposi's growth factor (FGF-4) as well as for the bFGF-related vascular endothelial growth factor, VEGF. No binding to epidermal growth factor (EGF) was observed. In addition, using a radioreceptor assay, we have shown that phosphorothioate homopolymers of cytidine and thymidine blocked binding of not only 125I-bFGF, but also of 125I-PDGF to NIH 3T3 cells, whereas phosphodiester oligodeoxynucleotides were ineffective. The extent of blockade of binding was dependent on the chain length of the phosphorothioate oligodeoxynucleotide. Furthermore, we have examined the effects of 18-mer phosphorothioate oligodeoxynucleotides of different sequences on 125I-bFGF binding to low and high affinity sites on both NIH 3T3 fibroblasts and DU-145 prostate cancer cells. Despite the fact that we have observed inhibition of bFGF binding by the 18-mer phosphorothioate oligodeoxynucleotides for both the high and low affinity classes of bFGF receptor, the inhibition was sequence-selective only for the high affinity receptors. We have also demonstrated that phosphorothioate homopolymers of cytidine and thymidine release bFGF bound to low affinity receptors in extracellular matrix (ECM). Finally, the most potent phosphorothioate oligodeoxynucleotides used in these experiments (e.g. SdC28) were inhibitors of bFGF-induced DNA synthesis in NIH 3T3 cells.

3T3 Cells↗
PubMed1995

Heparan sulfate primed on beta-D-xylosides restores binding of basic fibroblast growth factor.

Heparan sulfate proteoglycans (HSPG) are obligatory for receptor binding and mitogenic activity of basic fibroblast growth factor (bFGF). Mutant Chinese hamster ovary cells (pgsA-745) deficient in xylosyltransferase are unable to initiate glycosaminoglycan synthesis and hence can not bind bFGF to low- and high-affinity cell surface receptors. Exposure of pgsA-745 cells to beta-D-xylopyranosides containing hydrophobic aglycones resulted in restoration of bFGF binding in a manner similar to that induced by soluble heparin or by heparan sulfate (HS) normally associated with cell surfaces. Restoration of bF-GF binding correlated with the ability of the beta-D-xylosides to prime the synthesis of heparan sulfate. Thus, both heparan sulfate synthesis and bFGF receptor binding were induced by low concentrations (10-30 microM) of estradiol-beta-D-xyloside and naphthyl-beta-D-xyloside, but not by cis/trans-decahydro-2-naphthyl-beta-D-xyloside, which at low concentration primes mainly chondroitin sulfate. The obligatory involvement of xyloside-primed heparan sulfate in restoration of bFGF-receptor binding was also demonstrated by its sensitivity to heparinase treatment and by the lack of restoration activity in CHO cell mutants that lack enzymatic activities required to form the repeating disaccharide unit characteristic of heparan sulfate. Xyloside-primed heparan sulfate binds to the cell surface. Restoration of bFGF receptor binding was induced by both soluble and cell bound xyloside-primed heparan sulfate and was abolished in cells that were exposed to 0.5-1.0 M NaCl prior to the bFGF binding reaction. These results indicate that heparan sulfate chains produced on xyloside primers behave like heparan sulfate chains attached to cellular core proteins in terms of affinity for bFGF and ability to function as low-affinity sites in a dual receptor mechanism characteristic of bFGF and other heparin-binding growth promoting factors.

Animals↗
PubMed1995

Laminarin sulfate mimics the effects of heparin on smooth muscle cell proliferation and basic fibroblast growth factor-receptor binding and mitogenic activity.

Heparin and heparin-like molecules may function, apart from their effect on hemostasis, as regulators of cell growth and neovascularization. We investigated whether similar effects are exerted by laminarin sulfate, an unrelated polysulfated saccharide isolated from the cell wall of seaweed and composed of chemically O-sulfated beta-(1,3)-linked glucose residues. Laminarin sulfate exhibits about 30% of the anticoagulant activity of heparin and is effective therapeutically in the prevention and treatment of cerebrovascular diseases. We characterized the effect of laminarin sulfate on interaction of the heparin-binding angiogenic factor, basic fibroblast growth factor (bFGF), with a naturally produced subendothelial extra-cellular matrix (ECM) and with cell surface receptor sites. Laminarin sulfate (1-2 micrograms/ml) inhibited the binding of bFGF to ECM and to the surface of vascular smooth muscle cells (SMC) in a manner similar to that observed with heparin. Likewise, laminarin sulfate efficiently displaced both ECM- and cell-bound bFGF at concentrations as low as 1 microgram/ml. Both laminarin sulfate and heparin efficiently induced restoration of bFGF receptor binding in xylosyltransferase-deficient CHO cell mutants defective in initiation of glycosaminoglycan synthesis. Moreover, laminarin sulfate elicited bFGF receptor activation and mitogenic response in heparan sulfate (HS)-deficient, cytokine-dependent lymphoid cells. These results indicate that laminarin sulfate effectively replaced the need for heparin and HS in the induction of bFGF receptor binding and signaling. In other experiments, laminarin sulfate was found to inhibit the proliferation of vascular SMC in a manner similar to that observed with heparin. These effects of laminarin sulfate may have potential clinical applications in diverse situations such as wound healing, angiogenesis, and atherosclerosis.

Animals↗
PubMed1995

Differential effects of polysulfated polysaccharide on experimental encephalomyelitis, proliferation of autoimmune T cells, and inhibition of heparanase activity.

The extravasation of activated T lymphocytes through blood vessel walls and their migration to inflammatory loci are associated with secretion of extracellular matrix (ECM)-degrading enzymes, such as heparanase, which degrades heparan sulfate (HS) moieties of the ECM. The HS-degrading activity of heparanase was found to be inhibited by HS and heparin. Since induction of experimental autoimmune encephalomyelitis (EAE) requires extravasation and migration of autoimmune T cells, degradation of ECM by heparanase is expected to be involved in induction of the disease. Herein, we examined whether laminarin sulfate, a polysulfated polysaccharide (PSS) isolated from the cell walls of seaweeds and subjected to chemical sulfation, could inhibit ECM degradation by mammalian heparanase, and could prevent EAE. PSS was a more potent inhibitor of heparanase-mediated degradation of ECM than heparin. In-vivo, PSS, injected once a week, inhibited the severity of actively-induced EAE in rats. However, inhibition of EAE was not due to an overall suppression of autoimmune T cells, since PSS enhanced the proliferation of myelin basic protein (MBP)-specific, encephalitogenic T cells. PSS-activated autoimmune T cells, but not MBP-activated cells, failed to induce EAE in recipient rats. Moreover, rats injected with PSS-activated T cells were resistant to induction of EAE by anti-MBP CD4+ T cells. Thus, PSS may have potential clinical applications in the treatment of autoimmune diseases.

Animals↗
PubMed1994

Regulation of adhesion of CD4+ T lymphocytes to intact or heparinase-treated subendothelial extracellular matrix by diffusible or anchored RANTES and MIP-1 beta.

Chemokines, a superfamily of 8- to 11-kDa mediators of inflammation, affect the attachment of immune cells to vascular endothelia by binding to cell surface glycosaminoglycans. We analyzed whether chemokines are also involved in interactions between CD4+ T lymphocytes and the subendothelial extracellular matrix (ECM). Soluble mediators, such as MIP-1 beta and RANTES, induced the binding of resting human CD4+ T cells to ECM in an integrin-dependent manner. Both MIP-1 beta and RANTES bound to intact ECM and retained their adhesive properties, and moreover, ECM-bound RANTES and MIP-1 beta prolonged the time course of interactions between the CD4+ T cells and the ECM. Because the adhesive effect of these chemokines was restricted by an inhibitor of GTP-binding proteins, the adhesive effect of ECM-bound RANTES and MIP-1 beta, which requires an intact cytoskeleton, seems to involve activation of a G protein-linked receptor. MIP-1 beta and RANTES exert their pro-adhesive effects through interactions with glycosaminoglycans, because heparinase-treated ECM did not bound chemokines and because the chemokines ability to induce T cell adhesion was abrogated if: 1) either of the chemokines is pretreaed with heparin or heparan-sulfate (HS), 2) HS is removed from intact ECM by heparinase, an HS-specific endoglycosidase, or 3) the ECM-bound chemokines are released by pretreatment with heparinase. Hence, the adhesive effects of immobilized chemokines is not restricted to T cells interacting with endothelial cells, but also affects the migration of immune cells which reside and function in the context of ECM.

CD4-Positive T-Lymphocytes↗
PubMed1994

Variations in the size and sulfation of heparin modulate the effect of heparin on the binding of VEGF165 to its receptors.

The binding of the 165 amino-acid form of vascular endothelial growth factor (VEGF165) to the VEGF receptors of vascular endothelial cells was potentiated by heparin and heparan-sulfate, but not by other glycosaminoglycans. Heparin fragments of 16-18 sugar units inhibited the binding of 125I-VEGF165 to VEGF receptors, while fragments larger than 22 sugar units potentiated the binding. Over-sulfated heparin was a better potentiator of 125I-VEGF165 binding than native heparin. O-desulfated and N-desulfated heparins potentiated the binding to a lesser extent than native heparin. Heparin and N-desulfated heparin efficiently inhibited the binding of 125I-VEGF165 to alpha 2-macroglobulin, but surprisingly, O-desulfated heparin was an ineffective inhibitor. Since alpha 2-macroglobulin does not bind heparin, it follows that VEGF165 does not bind O-desulfated heparin efficiently. These results suggest that the mechanism by which heparin modulates the binding of VEGF165 to the VEGF receptors may require an interaction with cell surface heparin binding molecules.

Animals↗
PubMed1994

Protein kinase C mediates basic fibroblast growth factor protection of endothelial cells against radiation-induced apoptosis.

Basic fibroblast growth factor (bFGF) was found to protect bovine aortic endothelial cells against the lethal effects of ionizing radiation by inhibiting the programmed cell death (apoptosis) induced in these cells by radiation exposure. The involvement of the bFGF receptor tyrosine kinase in this function was demonstrated by abrogation of the radioprotective effect of bFGF by a specific inhibitor of the bFGF receptor tyrosine kinase, the tyrphostin AG213. The downstream signaling after stimulation of the bFGF receptor tyrosine kinase in bovine aortic endothelial cells involved translocation of the alpha isotype of cytoplasmic protein kinase C (PKC) into the membrane and its activation within 30 s after bFGF stimulation. The involvement of PKC in the radioprotective effect conferred by bFGF was suggested by the demonstration that nonspecific PKC activation by short-term exposure (30 min) to the phorbol ester, 12-O-tetradecanoylphorbol-13-acetate (TPA; 30 ng/ml) mimicked the radioprotective effect of bFGF. Furthermore, treatment of the cells with the PKC inhibitor 1-(5-isoquinolinesulfonyl)-2-methylpiperazine (20 microM) abrogated the radioprotective effect of bFGF, as was observed after the depletion of cellular PKC by overnight preincubation with high-dose TPA (200 nM). Agarose gel electrophoresis of DNA extracted from irradiated bovine aortic endothelial cells showed that both TPA (30 ng/ml; 30 min) and bFGF (1 ng/ml) inhibited the apoptotic degradation of DNA induced in these cells by radiation exposure (500 cGy). Both the bFGF- and the TPA-mediated inhibition of apoptosis could be reversed by the PKC inhibitor 1-(5-isoquinolinesulfonyl)-2-methylpiperazine (20 microM). These data demonstrate the involvement of PKC in the inhibition of radiation-induced apoptosis by bFGF and the rescue of endothelial cells from this mode of radiation-induced cell death.

Animals↗
PubMed1994

Differential structural requirements of heparin and heparan sulfate proteoglycans that promote binding of basic fibroblast growth factor to its receptor.

Heparan sulfate proteoglycans (HSPG) are obligatory for receptor binding and mitogenic activity of basic fibroblast growth factor (bFGF). The capacity of various species of heparin and heparan sulfate (HS) to promote bFGF receptor binding was investigated using both Chinese hamster ovary mutant cells deficient in cell surface HSPG and a soluble bFGF receptor-alkaline phosphatase fusion protein. Highly sulfated oligosaccharides were more effective than medium and low sulfate fractions of the same size oligosaccharide. O-Sulfation in heparin was found to be critical for its capacity to promote binding of bFGF to its receptors. The highest level of bFGF-receptor binding was achieved in the presence of over-sulfated heparin fragments (% sulfur > 14) regardless of whether the N-position was sulfated or acetylated. Unlike receptor binding of bFGF which requires oligosaccharides containing at least 8-10 sugar units, displacement of heparin- or HS-bound bFGF was obtained by oligosaccharides containing as little as four sugar units and by an N-sulfated, O-desulfated heparin fragment (% sulfur = 5.3). A preparation of total cell surface-derived HS induced bFGF receptor binding. A preliminary survey of several defined and affinity purified species of cell surface HSPG, including syndecan, fibroglycan, and glypican failed to identify natural HSPG that promote high affinity receptor binding of bFGF. A similar lack of activity was observed with species of HS isolated from bovine arterial tissue and characterized for their effect on vascular smooth muscle cell proliferation. Moreover, most of these species of HS inhibited in a dose-dependent manner the restoration of bFGF-receptor binding induced by heparin or by total HSPG. These results suggest the involvement of defined heparin-like oligosaccharide sequences and unique species of cell surface and extracellular matrix HS in the regulation of bFGF receptor binding and biological activity.

Animals↗
PubMed1994

Antiproliferative activity to vascular smooth muscle cells and receptor binding of heparin-mimicking polyaromatic anionic compounds.

Proliferation of bovine aortic smooth muscle cells (SMCs) induced by thrombin, basic fibroblast growth factor, or serum is inhibited by anionic, nonsulfated aromatic compounds that mimic many of the effects of heparin. Among these compounds are aurintricarboxylic acid (ATA) and a newly synthesized polymer of 4-hydroxyphenoxy acetic acid (compound RG-13577). Iodinated- or 14C-labeled compound RG-13577 binds to cultured SMCs in a highly specific and saturable manner. Scatchard analysis of the binding data revealed the presence of an estimated 1 x 10(7) binding sites per cell with an apparent dissociation constant of 3 x 10(-6) mol/L. Binding of radiolabeled RG-13577 was efficiently competed for by related aromatic anionic compounds and by apolipoprotein E, but not by heparin, heparan sulfate, suramin, or various purified growth factors and extracellular matrix proteins. Receptor cross-linking of SMC-bound 125I-RG-13577 revealed a single species of high M(r) (approximately 280 kD) cell surface receptors detected in the absence but not the presence of excess unlabeled compound RG-13577. Binding was susceptible to downregulation and restoration of receptor levels in a manner similar to that of hormone and growth factor receptors. We suggest that the antiproliferative activity of compound RG-13577 and related compounds is initiated by binding to specific growth-inhibiting cell surface receptors. Heparin-mimicking compounds may be applied to inhibit SMC proliferation associated with atherosclerosis and restenosis.

Animals↗
PubMed1994

Entactin/nidogen: synthesis by bovine corneal endothelial cells and distribution in the human cornea.

PURPOSE: The purposes of this study were to determine whether entactin/nidogen (E/N) is synthesized and secreted by corneal endothelial cells and to characterize the distribution of E/N in the human cornea. METHODS: Cultured bovine corneal endothelial cells were metabolically labeled with [35S]methionine. Newly synthesized E/N was detected in cell lysates and culture medium by immunoprecipitation, using monoclonal anti-E/N antibodies, polyacrylamide gel electrophoresis, and autoradiography. The presence of E/N in the subendothelial extracellular matrix was demonstrated by Western blot analysis of solubilized extracellular matrix proteins. The distribution of E/N in normal human corneas was studied by indirect immunofluorescent staining of frozen sections, using monospecific anti-E/N antibodies. RESULTS: E/N was detected in the basement membrane (BM)-like extracellular matrix deposited by corneal endothelial cells, as well as in cell lysates and culture medium. Immunofluorescence studies revealed the presence of E/N in both the epithelial and endothelial BM and to a much lower extent in the stroma. E/N was detected throughout the thickness of the epithelial BM, but its staining decreased in intensity toward the central part of the cornea. In the endothelial BM (Descemet's membrane), E/N fluorescence was limited to its most posterior portion, produced postnatally. CONCLUSIONS: Corneal endothelial cells synthesize and secrete E/N, E/N was found in both the epithelial and endothelial basement membranes but was primarily localized to the posterior portion of Descemet's membrane and the periphery of the epithelial BM. The authors suggest that E/N may be important in healing processes of corneal injuries and in the pathogenesis of diseases involving the postnatal region of Descemet's membrane.

Animals↗
PubMed1993

Effects of ionizing irradiation on endothelial cell transglutaminase.

The activity of transglutaminase (TG) was measured in cultures of bovine aortic and capillary endothelial cells (EC) following exposure to gamma-irradiation. Resting confluent EC express significant TG activity which fluctuates in growing cells. This activity was increased by 2-fold following non-lethal irradiation. The increase in TG activity was dose dependent up to 20 Gy and reached a plateau at 24-36 h after irradiation. Immunohistochemical studies showed a prominent increase in cytoplasmic TG following irradiation. Western blot analysis of whole cell extracts showed no increase in total cellular TG. Kinetic studies demonstrated that the affinity of the enzyme to its substrate was not altered, but the Vmax was increased. TG has previously been shown to be stored in an inactive form in EC membranes. This activity could be recovered in normal EC, but not in irradiated EC, by the addition of potassium thiocyanate and dithiothreitol or 0.8 M NaCl. An inhibitor of TG was previously demonstrated in the 100,000 x g particulate fraction of EC. Following irradiation, a significant decrease in this inhibitory activity was demonstrated. These results imply that the post-irradiation enhancement of TG activity may be caused by activation of a latent cellular enzyme. This elevated TG activity may cross-link adjacent cytoplasmic and membrane proteins and may thus play an active role in the enhanced apoptosis observed following irradiation of EC.

Animals↗
PubMed1993

Thrombin-induced release of active basic fibroblast growth factor-heparan sulfate complexes from subendothelial extracellular matrix.

The angiogenic factor, basic fibroblast growth factor (bFGF), is sequestered and protected by binding to heparan sulfate proteoglycans (HSPG) in the subendothelial extracellular matrix (ECM). Release of ECM-bound bFGF provides a novel mechanism for regulation of cell proliferation and neovascularization in normal and pathologic situations. Exposure of ECM to thrombin, the final activation product of the clotting cascade, resulted in release of high molecular weight HSPG-bFGF complex, as indicated by its immunoprecipitation with anti-bFGF antibodies, susceptibility to degradation by bacterial heparinase, and inhibition of its mitogenic activity in the presence of neutralizing anti-bFGF antibodies. The ECM-resident bFGF-HSPG complex was not released by thrombin in the presence of hirudin or antithrombin III, or by catalytically blocked thrombin preparations. A threefold to fivefold higher mitogenic activity was released by thrombin from ECM that was preheated (1 hour, 80 degrees C), as compared with native ECM. This difference is attributed to heat stable bFGF-HSPG complexes that are more readily released after heat treatment of the ECM and to activation and release of ECM-resident transforming growth factor-beta (TGF-beta) activity. Our results indicate that the large reservoir of proteolytic activity present in plasma in the form of prothrombin may participate in release from the subendothelial ECM of biologically active bFGF and TGF-beta, depending on the accessibility of thrombin. Thrombin may gain access to the subendothelium on clot formation after tissue injury and as a result of the conversion of prothrombin to thrombin induced by the ECM itself.

Animals↗
PubMed1993

Charge-dependent binding of granzyme A (MTSP-1) to basement membranes.

The murine T cell-associated serine proteinase granzyme A [also termed Murine T cell-associated serine proteinase-1 (MTSP-1), or SE-1] expresses optimal enzymatic activity under extracellular milieu conditions. It degrades a variety of proteins that are constituents of basement membranes. Granzyme A is harbored within intracellular storage granules from which its release can be induced by appropriate ligand binding to extracellular matrix receptors of T cells. Secreted granzyme A has, therefore, been implicated in the degradation of extracellular matrix barriers during T cell migration. Here we show that granzyme A binds to natural basement membranes in a charge-dependent manner. Binding of granzyme A to charged surfaces protects if from inhibition by natural high molecular weight inhibitors. The interaction of granzyme A with in vitro-produced extracellular matrices liberates basic fibroblast growth factor, which is bound to negatively charged heparan sulfate glycosaminoglycans of the extracellular matrix. We propose that the charge-dependent interaction of granzyme A with basement membranes has multiple, biologically relevant consequences.

Animals↗
PubMed1993

Extracellular matrix produced by cultured corneal and aortic endothelial cells contains active tissue-type and urokinase-type plasminogen activators.

Incubation of plasminogen with the subendothelial extracellular matrix (ECM) synthesized by cultured bovine corneal and aortic endothelial cells resulted in generation of fibrinolytic activity, indicated by proteolysis of 125I-fibrin in a time- and dose-dependent manner. Both tissue-type plasminogen activator (t-PA) and urokinase-type plasminogen activator (u-PA) were identified in the ECM by fibrin zymography, immunoblotting, and inhibition of plasminogen activation by anti-u-PA and anti-t-PA antibodies. Most of the ECM-resident plasminogen activator (PA) activity did not originate from intracellular PA release occurring when the endothelial cells were lyzed and the ECM exposed, since a comparable amount of PA was associated with the ECM when the cells were lyzed with Triton X-100 or removed intact by treatment with 2 M urea. Active u-PA and t-PA were released from ECM by treatment with heparanase (endo-beta-D-glucuronidase), indicating that some of the ECM-resident PA activity is sequestered by heparan sulfate side chains. These results indicate that both u-PA and t-PA produced by endothelial cells are firmly sequestered in an active form by the subendothelial ECM. It is suggested that ECM-resident plasminogen activators participate in sequential matrix degradation during cell invasion and tumor metastasis. PA activity may also function in release of ECM-bound growth factors (i.e., basic fibroblast growth factor) and activation of proenzymes (i.e., prothrombin), resulting in modulation of the ECM growth-promoting and thrombogenic properties.

Absorption↗
PubMed1993

An improved method of endothelial seeding on small caliber prosthetic vascular grafts coated with natural extracellular matrix.

The feature that clearly distinguishes natural blood vessels from their artificial counterparts is the presence of the endothelial cell lining that, besides being non-thrombogenic, is capable of repair and renewal. This study describes a method of coating vascular grafts with a uniform naturally produced subendothelial extracellular matrix (ECM) prior to implantation. Bovine aortic endothelial cells were seeded at a low density on untreated GORE-TEX, GORE-TEX that was precoated with ECM, or GORE-TEX that was first coated with fibronectin and then with ECM. The cells were maintained in the absence of fibroblast growth factor (FGF) and the cell number determined after 7 days in culture. Poor growth was observed on untreated GORE-TEX (6030 +/- 1030 cells/well), a 10-fold improved growth was observed on ECM coated GORE-TEX (59900 +/- 1560 cells/well) and best results were obtained on fibronectin-ECM precoated GORE-TEX (131000 +/- 21000 cells/well). The thrombogenicity of the ECM was reduced by a mild glutaraldehyde treatment, performed prior to seeding the cells, accompanied by a 40-50% reduced endothelial cell growth. These results indicate that ECM provides a suitable biolayer for endothelial cell adhesion, growth and differentiation. It contains both adhesion glycoproteins (fibronectin, laminin, collagen) and endothelial cell growth factors (basic fibroblast growth factor) that support adhesion and normal growth of suboptimal concentrations of endothelial cells. We suggest that the presence in ECM of both adhesive macromolecules and potent endothelial cell growth promoting factors will make the ECM a promising substrate for vascular grafts.

Animals↗