Areas of demyelination do not attract significant numbers of Schwann cells transplanted into normal white matter

If Schwann cell transplantation is to be used as a therapy for demyelinating disease, it is important to know if the number of transplanted cells and their transplantation site affects the extent of remyelination. Primary Schwann cell cultures were obtained from neonatal rat sciatic nerve, purified, and expanded using bovine pituitary extract and forskolin. Areas of persistent demyelination were created in the dorsal funiculus of the thoracolumbar spinal cord of rats by injecting ethidium bromide into white matter exposed to 40 Gy of X-irradiation, and a high and low number of Schwann cells were transplanted, into either the area of demyelination or the dorsal funiculus cranial to the area of demyelination. Animals were perfused 4 weeks after transplantation. After injection of 4 x 10(4) cells into the area of demyelination, the area of Schwann cell remyelination was 0.88 +/- 0.16 mm(2), while following the injection of 3 x 10(3) cells it was significantly smaller, 0.29 +/- 0.09 mm(2). After implantation of Schwann cells 1-3 mm (mean 2.5 mm) cranial to the area of demyelination, only one of the eight; animals (a high-dose animal) showed extensive Schwann cell remyelination. In this animal, the cells were transplanted within 1 mm of the area of demyelination, well within the length of tissue over which cells are passively spread by the injection procedure (1-3 mm). Our results show that significant numbers of transplanted Schwann cells are not attracted through normal tissue to areas of demyelination and when transplanted into areas of demyelination the extent of myelination is related to the number of Schwann cells transplanted. (C) 2000 Wiley-Liss, Inc.