Integration of transplanted cultured Schwann cells into the long myelinated fiber tracts of the adult spinal cord.
A suspension of about 10,000 purified Schwann cells cultured from the neonatal rat sciatic nerve was transplanted into a discrete site in the upper cervical level of the corticospinal tract of one side in adult rats. From 4 days after transplantation immunostaining for p75 (low-affinity neurotrophin receptor) showed that the transplants consisted of a central mass of Schwann cells and cuffs of elongated Schwann cells along the perivascular space of curving blood vessels (most of which had been formed in response to the transplantation). Schwann cells leaving the central mass and perivascular cuffs migrated in strictly linear orientation along the rostrocaudal axis of the host corticospinal tract. According to the territory through which they migrated, the transplanted Schwann cells adopted two quite different forms: (1) The row Schwann cells, which migrated singly or in groups within the rows of host oligodendrocytic and astrocytic cell bodies, were non-process-bearing, rather cuboidal, brick-like cells (about 8 x 12 microm in size). (2) In contrast, the interfascicular Schwann cells, which migrated singly or intertwined in rope-like small groups interspersed among the axons of the host corticospinal tract, were larger, symmetrically bipolar cells, with processes about 100-120 microm long and 2 microm wide and bulging, ovoid nuclei, located in centrally placed cell bodies about 10 microm across. After about 6 weeks, the p75 immunoreactivity of the interfascicular Schwann cells had become down-regulated. However, from as early as 10 days after transplantation, immunostaining for the peripheral myelin protein, P0, semithin sections, and electron microscopy showed that these Schwann cells were not lost, but that they had myelinated the segments of the host corticospinal axons in the region of the transplant. In contrast, the row Schwann cells did not express P0 or form myelin. They retained their p75 immunoreactivity at long survivals (presumably because they were secluded from contacting the tract axons). The row Schwann cells also migrated farther than the interfascicular Schwann cells (possibly a function of their maintained p75 expression), becoming dispersed singly for at least 8 mm from the original transplant site. Our previous study of corticospinal tract lesions had shown the formation of a "closed" scar formed by hypertrophic astrocytic processes, which walled off a central astrocyte-free region and totally disrupted the normal longitudinal alignment of the tract astrocytic processes. In contrast, while the present Schwann cell transplants induced a comparable astrocytic hypertrophy over the same time course, the astrocytic processes remained able to penetrate the transplant site, which was not walled off, so that the longitudinal arrangement of the host corticospinal tract astrocytic skeleton was preserved intact across the region of the transplant. These observations show that Schwann cells can be intimately integrated into the cytoarchitecture of the myelinated adult host corticospinal tract. This integration is not a random dispersal in damaged areas: it involves direct interaction with the cell elements present in the host tract, it respects the complex and regular organization of the host tract glial cells, and it results in the formation of a precisely arranged mosaic of central and peripheral tissue.
Li
Y
Y
Norman and Sadie Lee Research Centre, Laboratory of Neurobiology, National Institute for Medical Research, The Ridgeway, London, United Kingdom.
Raisman
G
G
D000367:Age Factors; D000818:Animals; D002465:Cell Movement / Q000502:physiology*; D002470:Cell Survival / Q000502:physiology; D005904:Glial Fibrillary Acidic Protein / Q000032:analysis; D007150:Immunohistochemistry; D008845:Microinjections; D008854:Microscopy, Electron; D009413:Nerve Fibers, Myelinated / Q000502:physiology* / Q000648:ultrastructure; D009416:Nerve Regeneration / Q000502:physiology; D009457:Neuroglia / Q000737:chemistry; D011712:Pyramidal Tracts; D051381:Rats; D012583:Schwann Cells / Q000166:cytology / Q000637:transplantation* / Q000648:ultrastructure; D012584:Sciatic Nerve / Q000166:cytology; D013997:Time Factors
D005904:Glial Fibrillary Acidic Protein