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Hematopoiesis on cellulose ester membranes: VII. Ultrastructure of stroma of marrow-enriched membranes with trilineal hematopoiesis.

The ultrastructure of developing osseous and hematopoietic tissue and supporting stroma was examined within intraperitoneally implanted, marrow-coated cellulose ester membranes (CEMs). During initial periods of implantation (two weeks), coated CEMs were shallowly infiltrated and surface-lined with mainly two stromal cell types--primitive mesenchymal cells and large, pleomorphic, multinucleated monocytoid-like stromal cells--and, in addition, endothelial cells in early stages of vessel development. Selective proliferation, maturation, and orientation of these cell types along the CEM's surface (one month), resulted in the formation of primitive osseous and hematopoietic tissue sites. Osseous sites developed as undifferentiated mesenchymal cells transformed into well-differentiated secretory cells residing in an electron-dense, pre-mineralized extracellular matrix, that upon extended implantation (3-6 months) formed bone. Hematopoietic sites developed as mesenchymal cells, in intimate contact with the monocytoid-like stromal cells, extended elongated branches into the medullary cavity, and enveloped newly formed surface-associated vascular structures. With subsequent maturation of vascular sinuses and supporting adventitial stroma (3-6 months), the sites were colonized with either uni-, bi-, or trilineal hematopoietic elements. These observations provide evidence that common, marrow-derived precursor stromal cells, i.e., mesenchymal and multinucleated monocytoid-like cells, cooperate in the development of both osseous and hemic tissue sites.