Grafting of cultured microglial cells into the lesioned spinal cord of adult rats enhances neurite outgrowth

There is contrasting in vitro and in vivo evidence regarding glial cell involvement in central nervous system (CNS) regeneration. This study has investigated the histological events that follow implantation of either microglia, mixed microglia/astrocytes, or astrocytes into the injured adult rat spinal cord. We have conducted an immunohistochemical characterization of the cellular profiles within and neuritic extension into various grafts consisting of gelfoam (GF) matrices impregnated with cultured microglia and/or astrocytes. After 2-5 weeks, prominent neuritic growth was observed into OX-42-immunoreactive (IR) microglial implants. These grafts were infiltrated by numerous host cellular elements including microvasculature and Schwann cells, and they demonstrated conspicuous laminin IR. Often, the patterns for laminin and OX-42 IR in microglial grafts were overlapping, suggesting partial expression of laminin on transplanted microglial cells. Mixed grafts of microglia and astrocytes demonstrated presence of neurites and laminin-IR elements with similar intensity as microglial grafts, while astroglial implants showed the least amount of neurite ingrowth. Some control implants consisting of cell-free GF showed marginal ingrowth of neurites in areas of infiltrating OX-42-IR host cells. Collectively, our findings support a neurite growth-promoting role of activated microglia and suggest that microglia may counteract mechanisms that inhibit CNS regeneration. It remains to be determined whether the observed neurite growth-promoting effects are mediated directly by grafted and/or endogenous microglia, or whether this occurs via the recruitment of host Schwann cells.