Distribution and morphology of transgenic mouse oligodendroglial‐lineage cells following transplantation into normal and myelin‐deficient rat CNS

Abstract

Glial cells from neonatal M␤P5 transgenic mice, which express bacterial ␤-galactosidase (lacZ) under control of the myelin basic protein (MBP) promoter (Gow et al, 1992), were transplanted into the spinal cord or cerebral hemisphere of immunosuppressed normal and myelin-deficient (md) rats in order to assess the ability of the donor cells to survive, migrate, and differentiate within normal compared with myelin-deficient central nervous system (CNS). LacZϩ cells were detected as early as 6 -7 days after transplantation into the low thoracic cord and by 10 days had spread rostrally to the brainstem and caudally to the sacral spinal cord. Initially, compact lacZϩ cells, lacking processes, were found associated with small blood vessels and with the glia limitans. Cells of this type persisted throughout the experiment. Later, lacZϩ cells with processes were seen along fiber tracts in the dorsal columns and, after intracerebral injection, subjacent to ventricular ependyma, as well as scattered in cerebral white and gray parenchyma. The extent of spread was comparable in md and normal rats, but in the md group, the success rate was higher, and more cells differentiated into process-bearing oligodendrocytes. Acceptance of xenografts in immunosuppressed recipients equaled that of allografts. The overall spread of grafted cells exceeded that of injected charcoal, indicating active migration. In contrast to earlier studies that identified oligodendrocytes based on morphology alone, this study has allowed us to identify and track oligodendrocytes based on myelin gene expression. We show some oligodendrocytes whose morphology is consistent with classical morphological descriptions, some that resemble astrocytes, and a class of compact perivascular oligodendrocyte-lineage cells that we suggest are migratory.

Intravenous administration of human embryonic stem cell-derived neural precursor cells attenuates cuprizone-induced central nervous system (CNS) demyelination

“…administration of hES‐NPCs reduced the demyelinating effect of cuprizone treatment in mice. Our findings build upon several previous studies describing the potential benefit of using oligodendrocyte progenitors to repair the brains of genetically demyelinated animals [22–25] or in experimental models of demyelination [9,21,26,27]. Moreover, this study is also complemented by recent studies by others that have shown systemic delivery of progenitor cells can be a viable strategy to provide therapeutic benefit in models of neurologic disease [28–33].…”

The Myelin Mutants as Models to Study Myelin Repair in the Leukodystrophies

“…2). In the md rat, in some cases almost the entire dorsal column can be myelinated at the site of engraftment [22,23,77]. In both the shi and md rat, myelin made by transplanted cells is characteristically thin, similar to that seen in endogenous remyelination.…”