Grafted Fetal Astrocytes Migrate from Host Thoracic Spinal Cord to Lumbar Cord and Medulla

Abstract

Transplantation of fetal central nervous system [CNS] into adult host CNS ameliorated lesion-induced behavioral and learning deficits (Bernstein and Goldberg, 1987, 1988b; Deckel et al, 1986; Dunnett et al, 1983a, b; Gage et al, 1986) and neuronal atrophy (Bregman et al, 1986; Sharp et al, 1986). Transplants were also efficacious in the treatment of Parkinson-like symptoms (Kamo et al, 1986; Sladek et al, 1987) produced by MPTP [l-methyl-4-phenyl-1,2,3,6–tetrahydropyridine] in monkeys and behavioral abnormalities resulting from chemical lesions of the nigrostriatal system in rats (Dunnett et al, 1983a; Dunnett et al, 1983b; Freed, 1983). The initial view of the mechanisms by which transplants affected the injured CNS focused on the formation of new neuronal circuits and release of transmitter substances by grafted neurons. It was recently demonstrated, however, that grafts of cultured astrocytes alone and transplants of Gelfoam removed from a wound cavity in the adult CNS were as efficacious in reversing a lesion-induced learning deficit as were grafts of fetal cerebral cortex (Kesslak et al, 1986). This is of interest since astrocytes in culture have been shown to produce a number of growth factors which support or enhance the survival and/or sprouting of neurons in culture (Assouline et al, 1987). Given this new avenue of research, we felt it was of considerable importance to determine whether transplant derived astrocytes could migrate more than the 1–3 mm previously reported by other investigators (Jacque et al, 1986; Raisman et al, 1985). If migration on the order of centimeters rather than millimeters was possible, then a significant role for astrocyte-derived neurotrophic factors could be envisioned in the regeneration/repair process after CNS injury by transplantation of these cells.