Migration of cells into and out of peripheral nerve isografts in the peripheral and central nervous systems of the adult mouse

Peripheral nerve (PN) isografts provide a favourable environment for axon r egeneration after peripheral and central nervous system (CNS) injury, but d efinitive information on the extent of cellular intermixing between donor a nd host tissues is lacking. We wished to compare migration patterns in fres h and predegenerate PN grafts, and also compare the extent of cell migratio n after transplantation to peripheral nervous system (PNS) versus CNS. To d iscern how host and donor cells interact after PIN transplantation, sciatic nerve segments were transplanted from inbred adult mice into PN defects (P N-PN grafts) or into lesioned cerebral cortex of opposite gender siblings. Migrating male cells were identified using a Y-chromosome-specific probe an d in situ hybridization methods, and characterized immunohistochemically. T he extent of donor and host cellular intermixing was similar in fresh and p redegenerate PN-PN isografts. There was substantial intermixing of donor an d host cells by 8 days. Many host cells migrating into epineurial regions o f grafts were immunopositive for F4/80 (macrophages). The endoneurium of gr afted PN was also colonized by host cells; some were F4/80(+) but many were immunostained with S-100 (Schwann cell marker). Donor S-100(+) Schwann cel ls rapidly migrated out into proximal and distal host PN and by 12 weeks we re found at least 2 mm from the grafts. Endoneurial microvessels in grafts were mostly donor-derived. By comparison, in male PN grafts to female CNS, even after 6 weeks few donor cells had migrated out into surrounding host c ortex, despite the observation that almost all grafts contained regeneratin g axons and were thus attached to host CNS tissue.