The hematopoietic microenvironment of the bone marrow: An ultrastructural study of the stroma in rats

Abstract

The bone marrow contains branching vascular sinuses lying in a fibroblastic stroma which supports hematopoiesis. This paper describes the stroma and vascular sinuses by scanning and transmission electron microscopy and in freeze-fracture etch replicas in normal rat femoral marrow and in rats made eosinophilic by larvae of trichinella spiralis. The stroma consists primarily of reticular cells which ensheath sinuses as adventitial cells and branch into the surrounding hematopoietic space. They form a spongework on which hematopoietic cells are arranged. Erythroblasts, clustered into islets, and megakaryocytes lie just outside sinuses. Granulocytes, until the metamyelocyte stage, lie in the midst of the hematopoietic cords. Lymphocytes, monocytes and likely stem cells, are clustered about arterial vessels. Macrophages occur throughout the marrow. Fat cells occur adventitial to vascular sinuses and appear to be reticular cells which accumulate fat. Processes of reticular cells closely envelope hematopoietic cells or protrude into them. Reticular cells contain rough ER and are likely fibroblastic. The argyrophilic reticular fibers of the marrow are, however, slender and scanty. Reticular cells are rich in filaments and they may contain many microtubules. They are not phagocytic and possess few lysosomes. The reticular cell cover of a vascular sinus is lifted away as maturing hematopoietic cells approach the sinus, preparatory to crossing the endothelium and entering the circulation. Maturing granulocytes often show microvilli on reaching the basal endothelial surface. The level of eosinophils in the marrow may increase from approximately four to more than 20% after injection of trichinella larvae. Close distinctive association of reticular cells and eosinophils are marked. Reticular cells provide a physical spongework on which hematopoietic cells are supported. But I postulate that they also trap and induce differentiation of hematopoietic stem cells, and sort the differentiating hematopoietic cells into characteristic locations in their spongework.