Role of axon-deprived Schwann cells in perineurial regeneration in the rat sciatic nerve.

The role of Schwann cells (SC) in perineurial regeneration after nerve injury has not yet been resolved. It was hypothesized that SC alone are able to induce at least partial morphological restoration of the destroyed orthotopic perineureum (PN). To test the hypothesis, a permanently denervated segment of the rat sciatic nerve was made acellular by freeze-thawing, except in its most proximal part where non-neuronal cells were left intact. Restoration of the frozen segment by these cells was examined by electron microscopy and immunohistochemistry of the SC marker, S-100 protein, 4 and 8 weeks after injury. The PN regenerated from undifferentiated fibroblast-like cells. In the presence of migrant SC without axons, regenerated cells in the place of the former PN were stacked in several layers and, in accordance with the hypothesis, partially expressed typical features of the perineurial cells (PC): pinocytotic vesicles, short fragments of basal lamina and tight junctions. Migrant SC induced formation of pseudo-minifascicles even in the epineurium. In these, SC organized the adjacent fibroblasts into a multilayered circular sheath, and induced their partial differentiation towards perineurial cells. Further experiments demonstrated that regenerating axons are required for complete morphological differentiation of the regenerated perineurial cells either in the orthotopic PN or in minifascicles.