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Therapeutic embolization of renal cell carcinoma.

The technique of embolization of renal cell carcinoma is assessed on the basis of the authors' experience. The procedure is usually envisaged in case of hypervascularized extracapsular tumors, with the purpose of obtaining the preoperative occlusion of the renal artery. Nevertheless, it cannot replace surgery, which can accomplish it with much more safety. The technique of embolization itself, which should be as selective as possible, is also discussed and its clinicobiological (immunological) implications are introduced.

Adenocarcinoma↗

Preoperative embolization of renal tumors--comparison of different methods.

Different techniques and materials for preoperative embolization of renal carcinoma have been assessed in 26 cases. The different methods used and compared were gelfoam fragments (10 cases), cyanoacrylate (4 cases), Gianturco stainless steel coil (3 cases) and the combination of gelfoam and the Gianturco device (9 cases). The method of choice appears to be the combination of gelfoam and the Gianturco device which allows excellent peripheral ischemia with complete occlusion of the main arterial trunks. Embolization is particularly useful in invading and hypervascularized renal tumors supplied by collateral blood vessels.

Bucrylate↗

A comparative study of the degree of arterial recanalization in kidneys of dogs following transcatheter embolization with eight different materials.

41 dogs were subjected to percutaneous arterial embolization of branches or the main trunk of the renal artery with or without prior injury to the kidney. 8 materials were used: homologous blood clot, muscle, fat, fascia, barium sulfate, plain catgut, gelfoam and polyvinyl alcohol (Ivalon). From the angiographic investigation over a relatively long period, it was observed that complete recanalization of the embolized vessels occurred only with blood clot and gelfoam; partial recanalization, with muscle fat and plain catgut; and no recanalization at all with fat, barium sulfate and Ivalon.

Adipose Tissue↗

Transcatheter arterial embolization of vesical artery in the treatment of invasive bladder cancer.

Transcatheter arterial embolization was performed in a total of 70 patients with invasive bladder cancer from October 1980 to December 1987. It was performed as a part of multidisciplinary treatment in patients with invasive bladder cancer. Microencapsulated mitomycin C, gelatin sponge and lipiodol (iodized oil) were used as the embolic material. As a result, reduction of tumor size was noted in 56.7%, but there was no embolic materials-related significant difference. Stage reduction was noted in 72.7% of patients where pathological stages were confirmed by operation. Hemostatic effects were noted in 76.5%. The symptoms of side effects included fever, leukocytosis, urinary frequency and pain, but none of them was severe. The results of the present study indicate that embolization of the vesical artery is useful in the treatment of bladder cancer.

Adult↗

Survival and function of bioengineered cardiac grafts.

INTRODUCTION: Patients with congenital heart disease frequently require graft material for repair of cardiac defects. However, currently available grafts lack growth potential and are noncontractile and thrombogenic. We have developed a viable cardiac graft that contracts spontaneously in tissue culture by seeding cells derived from fetal rat ventricular muscle into a biodegradable material. We report our investigations of the in vitro and in vivo survival and function of this bioengineered cardiac graft. METHODS AND RESULTS: A cardiomyocyte-enriched cell inoculum derived from fetal rat ventricular muscle was seeded into a piece of Gelfoam (Upjohn, Ontario, Canada), a biodegradable gelatin mesh, to form the graft. For in vitro studies, growth patterns of the cells within the graft were evaluated by constructing growth curves and by histologic examination; in in vivo studies, the graft was cultured for 7 days and then implanted either into the subcutaneous tissue of adult rat legs or onto myocardial scar tissue in a cryoinjured rat heart. Five weeks later, the graft was studied histologically. The inoculated cells attached to the gelatin mesh and grew in 3 dimensions in tissue culture, forming a beating cardiac graft. In both the subcutaneous tissue and the myocardial scar, blood vessels grew into the graft from the surrounding tissue. The graft implanted into the subcutaneous tissue contracted regularly and spontaneously. When implanted onto myocardial scar tissue, the cells within the graft survived and formed junctions with the recipient heart cells. CONCLUSIONS: Fetal rat ventricular cells can grow 3-dimensionally in a gelatin mesh. The cells in the graft formed cardiac tissue and survived and contracted spontaneously both in tissue culture and after subcutaneous implantation. Future versions of this bioengineered cardiac graft may eventually be used to repair cardiac defects.

Animals↗

Matrix embedding alters the immune response against endothelial cells in vitro and in vivo.

BACKGROUND: Endothelial cell (EC) dysfunction represents the first manifestation of atherosclerotic disease. Restoration of endothelium via seeding or transfection is hampered by local alterations in flow, inflammation, and metabolic activation. Perivascular EC matrix implants are shielded from these forces and still control vascular repair. The host immune response to such implants, however, remains largely unknown. We investigated the effect of embedding of ECs within 3-dimensional matrices on host immune responses in vitro and in vivo. METHODS AND RESULTS: We compared expression of major histocompatibility complex (MHC), costimulatory, and adhesion molecules by free aortic ECs or ECs embedded in Gelfoam matrices by flow-cytometry. T-cell proliferation was assessed by [3H] thymidine incorporation. Humoral immune response (ELISA and FACS analysis) and cellular (histopathology) infiltration were investigated after subcutaneous injection of free porcine aortic ECs (PAEs) or of a Gelfoam/EC block, or after concomitant injection of PAEs adjacent to Gelfoam in rats. Aortic ECs embedded in Gelfoam expressed lower levels of MHC class II, costimulatory, and adhesion molecules compared with free ECs (P<0.001), and induced 3-fold less proliferation of human CD4+ T-cells (P<0.0005). Implantation of a Gelfoam/EC block in rats nearly abrogated the immune response with 1.75- to 9.0-fold downregulation in tumor necrosis factor-alpha, interleukin-6, monocyte chemotactic protein-1, and PAE-specific immunoglobulin G (P<0.005) and 3.3- to 4.5-fold reduction in leukocytic tissue infiltration. Injecting PAEs adjacent to Gelfoam induced a significant response comparable to that of free implanted PAEs. CONCLUSIONS: Embedding ECs within 3-dimensional matrices alters the host immune response by inhibiting expression of MHC class II, costimulatory, and adhesion molecules, offering the rationale to develop novel therapies for vascular diseases.

Animals↗

Endothelial implants inhibit intimal hyperplasia after porcine angioplasty.

The perivascular implantation of tissue-engineered endothelial cells around injured arteries offers an opportunity to study fundamental vascular physiology as well as restore and improve tissue function. Cell source is an important issue because the ability to implant either xenogeneic or allogeneic cells would greatly enhance the clinical applications of tissue-engineered grafts. We investigated the biological and immunological responses to endothelial cell xenografts and allografts in pigs 4 weeks after angioplasty of the carotid arteries. Porcine or bovine aortic endothelial cells were cultured within Gelfoam matrices and implanted in the perivascular space of 42 injured arteries. Both porcine and bovine endothelial cell grafts reduced the restenosis index compared with control by 54% and 46%, respectively. Perivascular heparin release devices, formulated to release heparin at twice the rate of release of heparan sulfate proteoglycan from endothelial cell implants, produced no significant reduction in the restenosis index. Endothelial cell implants also reduced occlusive thrombosis compared with control and heparin release devices. Host immune responses to endothelial implants were investigated by immunohistochemical examination of explanted devices and by immunocytochemistry of serum samples. The bovine cell grafts displayed infiltration of leukocytes, consisting primarily of lymphocytes, and caused an increase in antibodies detected in serum samples. Reduced cellular infiltration and no humoral response were detected in animals that received allografts. Despite the difference in immune response, the biological effects of xenografts or allografts did not differ significantly.

Angioplasty↗

Collagen matrices enhance survival of transplanted cardiomyoblasts and contribute to functional improvement of ischemic rat hearts.

BACKGROUND: Cardiac cell transplantation is limited by poor graft viability. We aimed to enhance the survival of transplanted cardiomyoblasts using growth factor-supplemented collagen matrices. METHODS AND RESULTS: H9c2 cardiomyoblasts were lentivirally transduced to express firefly luciferase and green fluorescent protein (GFP). Lewis rats underwent ligation of the left anterior descending artery (LAD) ligation to induce an anterior wall myocardial infarction. Hearts (n=9/group) were harvested and restored ex vivo with 1 x 10(6) genetically labeled H9c2 cells either in (1) saline-suspension, or seeded onto (2) collagen-matrix (Gelfoam [GF];), (3) GF/Matrigel (GF/MG), (4) GF/MG/VEGF (10 microg/mL), or (5) GF/MG/FGF (10 microg/mL). Hearts were then abdominally transplanted into syngeneic recipients (working heart model). Controls (n=6/group) underwent infarction followed by GF implantation or saline injection. Cell survival was evaluated using optical bioluminescence on days 1, 5, 8, 14, and 28 postoperatively. At 4 weeks, fractional shortening and ejection fraction were determined using echocardiography and magnetic resonance imaging, respectively. Graft characteristics were assessed by immunohistology. Bioluminescence signals on days 5, 8, and 14 were higher for GF-based grafts compared with plain H9c2 injections (P<0.03). Signals were higher for GF/MG grafts compared with GF alone (P<0.02). GFP-positive, spindle-shaped H9c2 cells were found integrated in the infarct border zones at day 28. Left ventricular (LV) function of hearts implanted with collagen-based grafts was better compared with controls (P<0.05). Vascular endothelial growth factor or fibroblast growth factor did not further improve graft survival or heart function. CONCLUSIONS: Collagen matrices enhance early survival of H9c2 cardiomyoblasts after transplantation into ischemic hearts and lead to improved LV function. Further optimization of the graft design should make restoration of large myocardial infarctions by tissue engineering approaches effective.

Abdominal Cavity↗

Cytotoxicity evaluation of gelatin sponges prepared with different cross-linking agents.

Gelatin is a natural polymer used in pharmaceutical and medical applications, especially in the production of biocompatible and biodegradable wound dressings and drug delivery systems. Gelatin granules hydrate, swell and solubilize in water, and rapidly degrade in vivo. The durability of these materials could, however, be prolonged by cross-linking by aldehydes, carbodiimides, and aldose sugars, but the biocompatibility of collagenous biomaterials is profoundly influenced by the nature and extent of cross-linking. In this study, gelatin sponges were prepared by using various cross-linkers such as glutaraldehyde (GA), 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide hydrochloride (EDAC), and D-fructose. The effects of the type and the amount of cross-linker on thermal and mechanical properties, stability, and cytotoxicity were investigated. The mechanical analysis data showed that an increase in the amount of GA in the sponge structures caused a slight increase in the modulus of elasticity but had almost no effect on the tensile strength. Increase in the EDAC concentration produced a maximum in the modulus of elasticity and tensile strength values. The stability of the sponges and the time required for complete degradation in aqueous media increased in parallel with the cross-linker content. In vitro studies carried out with fibroblast cells demonstrated a higher cell viability for the samples cross-linked with low concentrations of GA than for those cross-linked with EDAC.

Biocompatible Materials↗

Diagnosis and determination of the clinical significance of type 1A laryngeal clefts by gelfoam injection.

Laryngeal clefts are rare congenital disorders, classified by multiple different schemes. Type IA (Armitage) and type I (Benjamin and Inglis) laryngeal clefts exhibit absence or hypoplasia of the interarytenoid muscles with an intact cricoid ring. Submucous or "occult" clefts occur with intact mucosa but absent underlying cartilage and/or muscle. Children with a diagnosis of posterior laryngeal cleft often have other congenital anomalies or medical disorders, including gastroesophageal reflux, tracheomalacia, syndrome complexes, and developmental delay. These associated disorders often confuse the diagnostic picture, as they may contribute to or account for the presenting symptoms of a laryngeal cleft. We propose a method to help clarify the clinical significance of the laryngeal clefts in these patients, and determine which patients would benefit from cleft repair. Eight patients with type IA laryngeal clefts are presented who were treated with a "test dose" Gelfoam injection into the interarytenoid area at the time of endoscopic diagnosis. All patients exhibited clinical improvement, and 4 patients showed improvement on the postinjection videofluoroscopic swallow study as compared to preoperative studies. One patient has gone on to surgical repair of the cleft after multiple injections. Endoscopic Gelfoam injection at the time of diagnosis can both alleviate symptoms and provide clarification of the posterior laryngeal cleft's contribution to the clinical status of the patient in these often complex cases.

Adult↗