Schwann cells transplanted into normal and x-irradiated adult white matterdo not migrate extensively and show poor long-term survival

Although Schwann cells are able to enter the central nervous system (CNS) w hen the integrity of the glia limitans is disrupted, their ability to migra te through intact CNS remains unclear. We have addressed this issue by tran splanting lacZ-labeled Schwann cells into normal adult spinal cord white ma tter, and into X-irradiated spinal cord tan environment that, unlike normal spinal cord, permits the migration of transplanted oligodendrocyte progeni tors). Schwann cell cultures, obtained from neonatal rat sciatic nerve and expanded using bovine pituitary extract and forskolin, were transfected by repeated exposure to retroviral vectors encoding the Escherichia coli lacZ gene, The normal behavior of the transduced cells was confirmed by transpla ntation into a nonrepairing area of demyelination in the spinal cord, where they formed myelin sheaths around demyelinated axons. A single microliter containing 4 x 10(4) cells was then transplanted into unlesioned normal and X-irradiated white matter of the spinal cord of adult syngeneic rats, One hour after injection, blue cells were observed as a discrete mass within th e dorsal funiculus with a longitudinal distribution of 2-3 mm, indicating t he extent of passive spread of the injected cells, At subsequent survival t imes (1, 2, and 4 weeks posttransplantation) blue cells had a distribution that was no more extensive than that seen 1 h after transplantation. Howeve r, the number of Schwann cells declined with time following transplantation such that at 4 weeks there were few surviving Schwann cells in both X-irra diated and nonirradiated spinal cord. These results indicate that transplan ted Schwann cells do not migrate extensively and show poor long-term surviv al when introduced into a normal CNS environment. (C) 2000 Academic Press.