Biomedical subjects

Amy Solan

Publications and source records attributed to Amy Solan.

7 recordsLinked to original sources

PubMed2005

Age effects on vascular smooth muscle: an engineered tissue approach.

Tissue engineering of blood vessels offers a potential new therapy for patients with vascular occlusive disease. In addition, tissue engineering technologies offer the opportunity to study the biology of vascular cells in a biomimetic, three-dimensional environment. A model for vascular tissue engineering was used to study the effects of vascular cell age on extracellular matrix (ECM) deposition, cellular mitosis, and protein synthesis under controlled conditions in vitro. Blood vessels were grown using a three-dimensional polyglycolic acid (PGA) mesh that was seeded with either infant or adult porcine vascular smooth muscle cells. Mechanical forces in the form of pulsatile radial distension were applied for the duration of the 7-week growth period. Overall, infant cells exhibited higher levels of cellular proliferation, ECM deposition, and remodeling activity than cells derived from adult animals. In addition, vessels cultured from infant cells had enhanced physical properties compared to vessels cultured from adult cells. The differentiation state of the smooth muscle cells in the infant and adult constructs was unchanged from the native state. However, the levels of immature pro-collagen, although undetectable in the vessels grown from adult cells, were similar in native vessels and in vessels grown with infant cells. These studies have important implications for the study of aging and vascular disease and remodeling, as well as for the field of tissue engineering.

Age Factors↗

PubMed2003

Gene therapy in tissue-engineered blood vessels.

Cardiovascular disease is the leading cause of morbidity and mortality in Western society. More than 1 million arterial bypass procedures are performed annually in the United States, where either autologous veins or synthetic grafts are used to replace arteries in the coronary or peripheral circulation. Tissue engineering of blood vessels from autologous cells has the potential to produce biological grafts for use in bypass surgery. Ex vivo development of vascular grafts also provides an ideal target of site-specific gene therapy to optimize the physiology of the developing conduit, and for the possible delivery of other therapeutic genes to a vascular bed of interest. In this article, we demonstrate that by using a novel retroviral gene delivery system, a target gene of interest can be specifically delivered to the endothelial cells of a developing engineered vessel. Further, we demonstrate that this technique results in stable incorporation of the delivered gene into the target endothelial cells for more than 30 days. These data demonstrate the utility of the retroviral gene delivery approach for optimizing the biologic phenotype of engineered vessels. This also provides the framework for testing an array of genes that may improve the function of engineered blood vessels after surgical implantation.

3T3 Cells↗

PubMed2003

Effect of pulse rate on collagen deposition in the tissue-engineered blood vessel.

The effect of mechanical stimulation on the development of tissue-engineered blood vessels was examined. In particular, three different rates of radial distension were chosen to produce a nonpulsed environment (0 beats per minute [bpm]), an adult heart rate (90 bpm), and a fetal heart rate (165 bpm). Engineered vessels were cultured for an average of 7 weeks. Vessel walls were then analyzed for collagen content and distribution. In addition, extracellular matrix remodeling was assessed through measurement of active matrix metalloproteinase type 1 (MMP-1) and tissue inhibitor of metalloproteinases type 1 (TIMP-1) levels. Vessels grown at a distension rate of 165 bpm had significantly higher collagen levels than those grown under static conditions. MMP-1 and TIMP-1 levels were also higher under pulsed conditions as compared with nonpulsed conditions. For the 90- and 165-bpm conditions, collagen and MMP-1 levels were not significantly different. TIMP-1 levels were significantly elevated at 165 bpm, indicating an increased cellular response to mechanical stimulation. Mechanical forces and their transduction represent a means to enhance the physical properties of artificial blood vessels, possibly by affecting the rate of extracellular matrix deposition and remodeling.

Animals↗

PubMed2003

Possible role for vascular cell proliferation in cerebral vasospasm after subarachnoid hemorrhage.

BACKGROUND AND PURPOSE: During vasospasm after subarachnoid hemorrhage (SAH), cerebral blood vessels show structural changes consistent with the actions of vascular mitogens. We measured platelet-derived vascular growth factors (PDGFs) in the cerebrospinal fluid (CSF) of patients after SAH and tested the effect of these factors on cerebral arteries in vivo and in vitro. METHODS: CSF was sampled from 14 patients after SAH, 6 patients not suffering SAH, and 8 normal controls. ELISA was performed for PDGF-AB, transforming growth factor-beta1, and vascular endothelial growth factor. A mouse model was used to compare cerebral vascular cell proliferation and PDGF staining in SAH compared with sham-operated controls. Normal human pial arteries were incubated for 7 days in vitro, 2 groups with human blood clot and 1 with and 1 without PDGF antibodies. RESULTS: PDGF-AB concentrations in CSF from SAH patients were significantly higher than those from non-SAH patients and normal controls, both during the first week after SAH and for all time points measured. Smooth muscle and fibroblast proliferation was observed after SAH in the mouse model, and this cellular replication was observed in conjunction with PDGF protein at the sites of thrombus. In human pial arteries, localized thrombus stimulated vessel wall proliferation, and proliferation was blocked by neutralizing antibodies directed against PDGFs. CONCLUSIONS: Vascular mitogens are increased in the CSF of patients after SAH. Proliferation of cells in the vascular wall is associated with perivascular thrombus. Cellular proliferation and subsequent vessel wall thickening may contribute to the syndrome of delayed cerebral vasospasm.

Adolescent↗

PubMed2002

Exploring the role of alanine in the structure of the Lac repressor tetramerization domain, a ferritin-like Alacoil.

We are interested in the determinants that specify the structure of antiparallel coiled coils. Antiparallel coiled coils often contain alanine as an important interfacial packing residue; structures containing alanine at certain well-defined positions in the heptad-repeating unit are referred to as Alacoils. Two types have been identified, containing alanine at either the g position of the heptad repeating unit (defined as the d position in the Richardson nomenclature), referred to as a rop-like Alacoil, or the e position (a position in the Richardson nomenclature), referred to as a ferritin-like Alacoil. The Lac repressor tetramerization domain forms an antiparallel four-chain coiled coil, which falls into the second class of Alacoils based on recent crystal structures. The role of alanine in such structures has not yet been explored experimentally. We test the importance of alanine at the e positions on the oligomeric state and stability of the isolated coiled-coil domain of Lac repressor by testing the effect of mutations at this position. We find that mutation to leucine is tolerated and its moderately stabilizing effect is most likely a consequence of plasticity of this motif. The effects on stability of the mutations to either serine or glutamine can be largely accounted for by helix propensity differences between these residues and alanine. The ability of the helices to adjust to such mutations, while maintaining the basic fold of this coiled coil, was further tested by making the same changes at the more highly exposed g position. Leucine at the g positions also causes an increase in stability, presumably by subtle rearrangement of the helices to allow partial desolvation of this side-chain.

Alanine↗

PubMed2002

Tissue engineering of the lymphatic system.

The field of tissue engineering has seen tremendous expansion in the last decade. In the last several years, tissue-engineering strategies to treat diseases of skin, cartilage, bone, bladder, blood vessel, tendon, and other tissues have been described. However, tissue-engineering approaches to treat diseases of the lymphatic system are currently nonexistent. We propose that acellular tissues, either native or engineered, could be exploited as a platform for the study of lymphatic biology, and for lymphatic tissue engineering. While speculative, this type of experimental model system could prove powerful for dissecting molecular and cellular events surrounding tumor invasion of lymphatics, as well as lymphangiogenesis. Scaffolds seeded with genetically engineered lymphatic cells could also be implanted to repopulate lymphatic vasculature. In the future, the lymphatic system will surely be added to the list of tissues and organs that prove amenable to tissue-engineering therapies.

Animals↗

PubMedDate not supplied

Blood vessels engineered from human cells.

Tissue engineering has made considerable progress in the past decade, but advances have stopped short of clinical application for most tissues. We postulated that an obstacle in engineering human tissues is the limited replicative capacity of adult somatic cells. To test this hypothesis, the effectiveness of telomerase expression to extend cellular lifespan was assessed in a model of human vascular tissue engineering. Telomerase expression in vascular cells isolated from elderly patients enabled the successful culture of engineered autologous blood vessels. Engineered vessels may one day provide a source of bypass conduit for patients with atherosclerotic disease.

Aged↗