The fate of Schwann cells transplanted in the brain during development

Purified rat Schwann cells labeled with Hoechst 33342 fluorescent fluorochrome were transplanted into the brain of the newborn shiverer mouse. The grafted cells survived and were able to migrate through the host parenchyma. However, Schwann cell migration was restricted to the grafted hemisphere and to structures adjacent to the graft. With time, Hoechst labeled cells, present at the site of implantation or dispersed in the host parenchyma, decreased progressively in number. Instead, they concentrated along the blood vessels, meninges and ventricles. Despite the presence of Hoechst labeled Schwann cells in white matter tracks during the process of central myelination, Schwann cell myelination could not be evidenced by immunodetection of the peripheral myelin protein or by ultrastructural observation of the typical Schwann cell basement membrane surrounding peripheral myelin. A series of additional transplantations involving Schwann cells of mouse or rat origin, grafted either as cell suspensions or as nerve fragments, demonstrated that transplanted Schwann cells formed myelin around developing host axons only when included in a nerve fragment. Immunodetection of GFAP in astrocytes and type IV collagen in basement membranes as well as electron microscopy showed that reactive astrocytes invaded the grafted area after the first week of transplantation and sometimes formed basement membranes isolating partially the graft from the host parenchyma. During host myelination, astrocytes, which were present in most white matter structures, surrounded grafted cells. Occasionally, they enclosed Schwann cells in basement membranes or encircled host axons. Later, reactive astrocytes were associated with Schwann cells restricted to blood vessel and ventricular walls, and meninges. Our results suggest that in the presence of competitive developing oligodendrocytes, astrocytes are able to limit migration and prevent myelination of Schwann cells transplanted in the newborn shiverer brain. In addition, astrocytes seem to be able to expel the grafted cells and finally exclude them from the host parenchyma.