Organisation of experimental thrombosis by blood cells

Abstract

To clarify whether thrombus organisation was carried out by local cell activity or by elements of the circulating blood we developed an artificial prosthesis, made of an impermeable polyurethane material with an athrombogenic surface but with a central part consisting of a DACRON velour ring which was thrombogenic. We implanted these devices into the aorta of 10 sheep. In these animals, organisation of the central thrombus by local aortic cells could be excluded. After varying periods of time (2-84 days), the device was removed and the organized thrombus investigated by light and electron microscopy. From our investigations the organisation process with the development of mesenchymal cellular elements proceeded in 3 steps: The activation of the mononuclear macrophage system, the appearance of myofibroblastic cells and endothelial formation. The activation of the mononuclear macrophage system is probably induced by chemospecific products of metabolism arising from aging thrombotic material. Apart from mononuclear elements such as monocytes, macrophages, and giant cells we observed fibroblast-like and myofibroblast-like cells. The matrix contained collagen. Endothelium developed on the surface of the organizing thrombus. The final stage was characterized by the formation of a pseudovessel wall, which followed the pattern of the vascular model. Our findings support the hypothesis that a thrombus may be organized by cells derived from the circulating blood.

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.…”

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

“…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? They might invade the thrombus from the adjacent circulating blood or they may be included in the clotting process from the very beginning together with granulocytes and other white blood cells.…”

Circulating Bone Marrow Cells Can Contribute to Neointimal Formation

“…Studies of physically isolated experimental arterial thrombus have indicated that some mesenchymal elements responsible for vascular healing might be derived from the circulating blood [6, 7]. Certainly, SMC in organizing arterial thrombi first appear on the luminal surface rather than the abluminal side adjacent to the media [6, 8].…”

“…Studies of physically isolated experimental arterial thrombus have indicated that some mesenchymal elements responsible for vascular healing might be derived from the circulating blood [6, 7]. Certainly, SMC in organizing arterial thrombi first appear on the luminal surface rather than the abluminal side adjacent to the media [6, 8]. Different lines of evidence have confirmed the existence of bone marrow pluripotent mesenchymal cells that can serve as a continuing source of progenitor cells for a variety of nonhematopoietic tissues and participate in tissue healing [9, 10, 11].…”