Directed migration of transplanted glial cells toward a spinal cord demyelinating lesion

To investigate the migration of transplanted glial cells in normal adult mice with a focal demyelinating lesion, we have used A2G mice which have the autosomal dominant Mx-1 allele as donor. Mx-1 protein expression is inducible by interferon and is detected in a dotted pattern in the nucleus of A2G cells. A/J mice were used as recipient animals as they express the same major histocompatibility antigens as A2G but cannot express the Mx-1 protein. An acute demyelinating lesion was produced in the A/J spinal cord by intraspinal injection of lysolecithin. Mixed glial cultures derived from newborn A2G brain were treated with alpha/beta interferon for 24 hr. These Mx-1 expressing glial cells were then transplanted two intervertebral spaces away from the demyelinating lesion. The fate of the grafted cells was followed over the next 13 days, during which the induced Mx-1 protein can still be detected by immunocytochemistry. Grafted cells were found between the transplantation site and the lesion at 24 hr and some of the Mx-1+ cells reached the lesion at 4 days. The majority of the Mx-1+ migrating cells expressed GFAP and were located in the myelinated white matter and around the blood vessels. Scattered MBP+, Mx-1+ cells were detected in the lesion indicating that some of the transplanted cells may participate in the repair process. The Mx-1 is a useful marker to follow the migration events in the days after grafting and to determined what factors may attract transplanted cells toward a demyelinating lesion.