Study On the Organization of Experimental Thrombi

Abstract

Organization of thrombi is believed to be due to the migration of cells from the vessel wall, but there is evidence from several sources that cells of the blood are also concerned.The organization of thrombi has always been attributed to fibroblasts. However, Haustl and others have recently identified smooth muscle cells in arteriosclerotic plaques. Hullinger2 as well as PaU13 has shown that blood cells may differentiate into fibroblasts, which have been repeatedly identified in organizing thrombi. Dible4 has described endothelial-lined channels in a thrombus which had no continuity with the lining endothelium of the vessel. Ghani and Tibbs5 thought that the new intimal and fibrous tissue lining a plastic arterial prosthesis had originated from blood-borne cells. Stamps and others have demonstrated that endothelium can form from cells circulating in the blood. We present here further evidence of the role played by cells of the circulating blood in the organization of thrombi and compare organization of thrombi isolated from, and in contact with, the vein wall. EXPERIMENTAL METHODSArtificial thrombi were formed using homologous dog's blood employing the technique first described by Chandler.7 A cylindrical container was produced by rolling a piece of dialyzing membrane 1-in long and V4 in in diameter. One end was securely tied by means of a linen thread. The formed thrombus was washed in normal saline and carefully placed in the container. A small amount of serum, including the buffy coat, was added to the thrombus and the container closed with a second linen ligature. A 10-cm length of the dog's femoral vein was dissected free and isolated between bulldog clamps. The container was introduced through a longitudinal incision and secured with a silk suture. Closure of the incision was performed transversely to avoid any stenosis. The bulldog clamps were removed and the wound was closed. After intervals of 1, 2, 3 and 4 weeks, the dogs were killed and the femoral veins, including the containers, were removed. The tissue was fixed in 10 per cent formal-saline; serial sections were cut and stained with hematoxylin and eosin.A second series of experiments were performed in which mural thrombi were produced in the inferior venae cavae of rabbits by the insertion of nylon gutat University of Manitoba Libraries on June 25, 2015 ang.sagepub.com Downloaded from

Differentiation of Mononuclear Blood Cells into Macrophages, Fibroblasts and Endothelial Cells in Thrombus Organization

“…A few days after the onset of blood clotting mononuclear cells are ob served in increasing numbers throughout the thrombus. This behaviour is independent of contact with the intimai layer and occurs even if the thrombus is completely separated from the vascular wall by experimental de vices [1,2,5], Mononuclear blood cells as well as granulocytes are believed to derive from a common undifferentiated precursor in the bone marrow [6][7][8], their life span is 36-72 h [6], They possess the capacity to dif ferentiate into endothelial cells, macro phages, giant cells, fibroblasts and even smooth muscle cells [5,8]. Their role in the vascularization of thrombi and emboli has been described earlier [5,11,12], How do these cells get into the thrombus?…”

“…Mononuclear blood cells are important for angiogenesis in organizing thrombi and emboli [1][2][3][4]. A few days after the onset of blood clotting mononuclear cells are ob served in increasing numbers throughout the thrombus.…”

Hemangioblasts, angioblasts, and adult endothelial cell progenitors

“…Beginning in 1967 several morphological studies suggested that monocytes could differentiate into endothelial cells to form intrathrombus capillaries (Tsapogas et al, 1967;Prathap, 1972;Feigl et al, 1985;Leu et al, 1987). Recent evidence that monocytes also act as endothelial progenitors cells comes from data showing that they can drill channels in the myopathic heart and that monocytes could take on an endothelial cell-like phenotype in vitro (Fernandez Pujol et al, 2000;Moldovan et al, 2000;Harraz et al, 2001;Schmeisser et al, 2001 (Fig.…”