Schwann cells transplanted into normal and X-irradiated adult white matter do not migrate extensively and show poor long-term survival.
Although Schwann cells are able to enter the central nervous system (CNS) when the integrity of the glia limitans is disrupted, their ability to migrate through intact CNS remains unclear. We have addressed this issue by transplanting lacZ-labeled Schwann cells into normal adult spinal cord white matter, and into X-irradiated spinal cord (an environment that, unlike normal spinal cord, permits the migration of transplanted oligodendrocyte progenitors). 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 transplantation 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 the dorsal funiculus with a longitudinal distribution of 2-3 mm, indicating the extent of passive spread of the injected cells. At subsequent survival times (1, 2, and 4 weeks posttransplantation) blue cells had a distribution that was no more extensive than that seen 1 h after transplantation. However, the number of Schwann cells declined with time following transplantation such that at 4 weeks there were few surviving Schwann cells in both X-irradiated and nonirradiated spinal cord. These results indicate that transplanted Schwann cells do not migrate extensively and show poor long-term survival when introduced into a normal CNS environment.
Department of Clinical Veterinary Medicine, University of Cambridge, Madingley Road, Cambridge, CB3 0ES, United Kingdom.
Y
Y
Iwashita
J W
JW
Fawcett
A J
AJ
Crang
R J
RJ
Franklin
W F
WF
Blakemore
D000818:Animals; D002452:Cell Count / Q000187:drug effects / Q000528:radiation effects; D002465:Cell Movement / Q000502:physiology / Q000528:radiation effects; D002470:Cell Survival / Q000502:physiology / Q000528:radiation effects; D002478:Cells, Cultured; D003711:Demyelinating Diseases / Q000139:chemically induced / Q000473:pathology; D004996:Ethidium; D005260:Female; D017930:Genes, Reporter / Q000235:genetics; D006085:Graft Survival / Q000502:physiology* / Q000528:radiation effects; D009186:Myelin Sheath / Q000378:metabolism; D009413:Nerve Fibers, Myelinated / Q000187:drug effects / Q000473:pathology / Q000528:radiation effects; D051381:Rats; D011917:Rats, Inbred Lew; D012583:Schwann Cells / Q000166:cytology / Q000378:metabolism / Q000637:transplantation*; D013116:Spinal Cord / Q000166:cytology* / Q000528:radiation effects*; D014162:Transfection; D001616:beta-Galactosidase / Q000235:genetics
D001616:beta-Galactosidase; D004996:Ethidium