Transplanted hMNPs promote histological recovery and alter intracellular signaling pathways.

(a) hMNP transplantation enhanced sprouting of endogenous serotonergic (5-HT) projections. hMNP-transplanted animals consistently contained aberrant projections throughout the dorsal gray matter (top panels, arrows) and dense innervation of the ventral horns (bottom panels) at 2 mm cranial to the injury site (b) At 2 mm and 3 mm cranial to the injury epicenter, and 1 mm caudal to the injury epicenter, 5-HT immunoreactivity was significantly greater than that observed in control animals. At 1 mm cranial to the injury epicenter, and 2 mm and 3 mm caudal to the injury epicenter, 5-HT immunoreactivity was not significantly different than in control animals. (c) NeuN immunostaining demonstrated that hMNP transplantation enhanced survival of endogenous (human nuclear antigen-negative) neurons 2 mm cranial to the injury site. (d) Quantification of enhanced neuronal survival in hMNP-transplanted animals cranial and caudal to the injury site. (e) hMNP transplantation attenuated phosphorylation of stress-associated protein kinase (SAPK). (f) Densitometric quantification of SAPK normalized to actin controls showed that 1 and 4 days following transplantation, phosphorylation of SAPK decreased in hMNP-transplanted animals relative to controls; no significant differences were observed between groups at 7 and 10 days. Bar = 200 µm for (a), 100 µm for (c).