The Fate of Schwann Cells Transplanted in the Brain during Development

Abstract

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 parenchyme. 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 parenchyme, 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 parenchyme. 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 expell the grafted cells and finally exclude them from the host parenchyme.

Olfactory ensheathing cells: Historical perspective and therapeutic potential

“…OECs are also becoming increasingly easier to obtain from extracranial sources, such as from human peripheral olfactory tissue or from similar tissue in the nasal cavity of rodents (Lu et al, 2001(Lu et al, , 2002Franklin, 2002b), thus providing the attractive proposition of a patient having the opportunity to provide their own olfactory tissue for autologous transplantation. Furthermore, the available evidence supports the view that OECs are more likely to integrate into the CNS parenchyma after grafting to repair the injured or demyelinated spinal cord (Li et al, 1998;Lakatos et al, 2000) than are Schwann cells (Baron-Van Evercooren et al, 1992;Blakemore, 1992;Duncan and Milward, 1995), as suggested by Doucette (1990Doucette ( , 1995 several years ago. One possible explanation for the failure of Schwann cells to integrate as easily into the CNS parenchyma is that astrocytes are known perturb the neuron-Schwann cell interactions normally leading to myelination (Franklin et al, 1992;Guenard et al, 1994b), and these cell-cell interactions appear also to inhibit the migration of Schwann cells toward the site of injury (Fawcett and Asher, 1999).…”

“…Cellular migration of Schwann cells within the CNS parenchyma is also limited. For example, when they are transplanted into the cerebral hemisphere of newborn shiverer mice, the migration is mostly confined to the vicinity of the graft; the grafted Schwann cells are also eventually extruded from the CNS parenchyma (Baron- Van Evercooren et al, 1992). It has been suggested that astrocytes inhibit the migration of Schwann cells within the parenchyma of the CNS (Fawcett and Asher, 1999).…”

Schwann Cells Are Removed from the Spinal Cord after Effecting Recovery from Paraplegia

“…Although not all studies have followed Schwann cell survival for the time period of this study, it is generally believed that Schwann cells, once in the CNS, form a stable population ( Baron-Van Evercooren et al, 1992). The displacement of Schwann cells in the present model is therefore surprising, and the mechanism underlying this event remains to be determined.…”

“…For Schwann cells to be considered as a viable therapy for central demyelinating conditions, in addition to being capable of remyelinating large areas of the cord (Scolding et al, 1998), they would have to restore debilitating motor functional deficits of the type resulting from large-scale demyelination. Finally, after remyelinating CNS axons, Schwann cells have to be capable of long-term survival in the CNS to ensure permanent recovery of function, an issue that remains unresolved ( Baron-Van Evercooren et al, 1992;Dusart et al, 1992).…”

Molecular Reconstruction of Nodes of Ranvier after Remyelination by Transplanted Olfactory Ensheathing Cells in the Demyelinated Spinal Cord

“…A number of cell types, including oligodendrocyte progenitors (Duncan et al, 1988;Keirstead et al, 1999Keirstead et al, , 2005Cao et al, 2005), Schwann cells (Blakemore and Crang Baron-Van Evercooren et al, 1992;Honmou et al, 1996), OECs (Franklin et al, 1996;Imaizumi et al, 1998;Barnett et al, 2000;Kato et al, 2000;Sasaki et al, 2004), and neural stem cells (Brustle et al, 1999;Akiyama et al, 2001), have been used to remyelinate central axons. However, an important prerequisite for recovery of action potential conduction in remyelinated axons is the appropriate organization of ion channels at nodes of Ranvier.…”