Uso de fibrinógeno humano en la generación de soportes para la obtención de equivalentes tisulares / Use of human fibrinogen in the generation of scaffold for obtaining Tissue equivalents

Desde sus orígenes, la Ingeniería de Tejidos ha buscado diversos materiales que puedan ser utilizados para la generación de soportes que sirvan para el anclaje, proliferación y diferenciación celular que conduzcan a la obtención de tejidos humanos. Muchos materiales de tipo cerámico, polimérico y metálico se han evaluado, pero hasta la fecha muchos de ellos han sido rechazados por diversas razones, entre otras su escasa biocompatibilidad y biodegradabilidad, la respuesta inmune generada, la baja resistencia mecánica o el riesgo de transmisión de virus o priones. El fibrinógeno es una proteína presente en el plasma sanguíneo que puede ser utilizada para la generación de soportes tridimensionales que favorezcan el crecimiento de células; se obtiene a partir del propio paciente, bancos de sangre o como proteína purificada (Tisseel® o Tissucol®, Laboratorios Baxter). El fibrinógeno evita el desencadenamiento de una respuesta inmunológica y el uso de productos xenogénicos. Debido a la estructura proteica, la adhesión y proliferación celular se ven favorecidas dando excelentes resultados en la generación de equivalentes de piel, cartílago, córnea y reemplazos cardiacos en aplicaciones in vitro e in vivo. Como desventajas presenta su rápida degradación y su baja resistencia mecánica; sin embargo, en los últimos años se han venido evaluando mezclas con algunos biopolímeros como ácido poliláctico (PLLA), ácido poli-glicólico (PGA) y alginato de sodio. Esta revisión presenta algunas de las principales aplicaciones del fibrinógeno en Ingeniería de Tejidos.

Since its origin, Tissue Engineering has sought various materials that can be used for generation of scaffolds that serve to anchor, proliferation and cell differentiation leading to the production of human tissues. Many materials such as ceramic, polymeric and metal type have been evaluated to date but many have been rejected for various reasons, including its limited biocompatibility and biodegradability, immune response generated, low mechanical strength or the risk of transmission of virus or prions. Fibrinogen is a protein present in blood plasma that can be used to generate three-dimensional scaffolds that favors growth of cells, it is obtained from the patient itself, bank of blood or purified protein (Tisseel® or Tissucol®, Laboratorios Baxter). Fibrinogen acts slowing or reversing the immune response and avoiding the use of xenogeneic materials. Because the protein structure, adhesion and cell proliferation is favored with excellent results in the generation of skin equivalents, cartilage, cornea and even heart replacements in vitro and in vivo. The disadvantages presented are the rapid degradation and low mechanical strength, but in recent years it has been evaluating some biopolymer mixtures as polylactic acid (PLLA), poly-glycolic acid (PGA) and sodium alginate. This review presents some of the main applications of fibrinogen in Tissue Engineering.

Lung lesions in human leptospirosis: microscopic, immunohistochemical, and ultrastructural features related to thrombocytopenia.

Lung fragments from 12 patients were collected immediately after death and studied by light and electron microscopy and by immunohistochemistry to describe the main morphologic and ultrastructural aspects of the lung and platelets in leptospirosis (Weil's syndrome), to search for the possibility of disseminated intravascular coagulation (DIC), and to assess the relationship between endothelial lesions and local platelet aggregation and the leptospiral antigen distribution, as well as its relationship with the intensity of the lesions. The immunohistochemical results for fibrin aggregates were positive in the lumen and/or on the vascular endothelium in nine cases and on the alveolar surface in seven cases, leading to the diagnosis of the adult respiratory distress syndrome in these seven cases. Test results for leptospiral antigen by immunohistochemistry were positive in eight cases with no direct relationship between antigen deposits in the pulmonary vascular endothelium and intensity of the lesions. The ultrastructural findings were uniform and constant. Capillary lesions were characterized by swelling of endothelial cells, an increase in pinocytotic vesicles, and giant dense bodies in the cytoplasm of these cells. No necrosis, rupture, nor exposed subendothelial collagen was observed outside the hemorrhagic areas, and the intercellular junctions were preserved. The lung involvement in severe human leptospirosis presents as hemorrhagic pneumopathy with septal capillary lesions that are the usual cause of death. The thrombocytopenia that was verified in 11 of 12 patients in our study seems to bear no relationship to DIC and seems to be determined by activation, adhesion, and aggregation of platelets to the stimulated vascular endothelium, with an amorphous electron-dense substance between the endothelial cells and the adherent platelets in places where the subendothelial collagen was not exposed.

Histochemical study of the villous fibrinoid material in the human full-term placenta

Fibrinoid material from human placental villi was investigated employing histochemical methods. According to the present results, the fibrinoid material seems to consist of glucoproteins containing a neutral mucopolysaccharide and a protein.This protein contains arginine, tyrosine, tryptophan and cysteine. The fibrinoid material displayed histochemical reactions very similar to those of fibrin. However, the insensity of the reactions was always higher in the fibrinoid substance. Histological staininng appears to be more effective in differentiating fibrinoid from fibrin

Anticuerpos antifosfolípidos: aspectos inmunoquímicos y patogénicos / Antiphospholipid antibodies: immunochemistry and pathogenetic features

Los anticuepos antifoslípidos (AFL), incluyen varios tipos como los que se describieron inicialmente en las enfermedades infecciosas. Además, se conocen ahora otros AFL como son los reactivos contra cardiolipina o los denominados anticoagulante de lupus. Estos AFL pueden ser isotipo IgG,M o A, la mayor relevancia actualmente se confiere al isotipo IgG. La especificidad parece estar dirigida a fosfolípidos con carga negativa y juega un papel importante a Apolipoproteína H como cofactor o integrante del complejo antigénico reconocido por una proporción de estos AFL. El impacto patogénico de estos AFL no se ha definido con certeza, pero la evidencia muestra intervención potencial en las fases de la coagulación dependientes de fosfolípidos

Evaluation of indium-111-labeled anti-fibrin antibody for imaging vascular thrombi.

Monoclonal antibody 59D8 developed by Hui et al., binds to fibrin but not fibrinogen. An 111In-labeled Fab fragment of 59D8 was studied in vitro and in animal models to evaluate its potential for imaging thrombi and emboli in man. Rabbits and dogs were used as models for studying thrombus uptake in vivo. Thrombi and emboli up to 4 days old were successfully visualized at 4-24 hr postinjection in five of eight rabbits. In dogs, 0.5-hr-old and 24-hr-old thrombi were successfully imaged at 24 hr in six of eight animals, and 3/6 of these were positive at 3-4 hr postinjection. Thrombus-to-blood ratios in the dogs averaged 7.1 +/- 1.3. The findings suggest this antibody may be useful for imaging thrombi in man.