Cell adhesion molecule l1-transfected embryonic stem cells with enhanced survival support regrowth of corticospinal tract axons in mice after spinal cord injury

Abstract

Previous studies have indicated that the cell adhesion molecule L1 enhances neuronal survival and neurite outgrowth. L1-mediated promotion of neurite outgrowth has been shown to occur also in an inhibitory environment not only in vitro, but also in vivo. To further investigate the effects of L1 in spinal cord injury, we transfected embryonic stem cells with a plasmid encoding the full-length mouse L1 molecule under the control of PGK promoter. An embryonic stem cell line derived from C57BL/6J transgenic mice that express green fluorescent protein under control of the beta-actin promoter was transfected with L1 and injected into the lesion site of 3-month-old C57BL/6J female mice 7 days after compression injury. Non-transfected embryonic stem cells were detectable at the lesion site 3 days after transplantation, but lost their cellular integrity 7 days after transplantation and were barely detectable 1 month after transplantation. In contrast, L1-transfected embryonic stem cells were detected 1 month after transplantation in numbers comparable to those of the injected cells and demonstrated extended processes. Further, in contrast to the few detectable nontransfected stem cells that remained at the injection site 1 month post-transplantation, the L1-transfected embryonic stem cells had migrated rostrally and caudally from the lesion. Anterogradely labeled corticospinal tract axons showed interdigitation with L1-transfected embryonic stem cells and, in contrast to non-transfected stem cells, extended into the lesion site 1 month after transplantation and, in some cases, extended beyond it. Our observations encourage the use of L1-transfected embryonic stem cells that express L1 not only at the cell surface, but also as a soluble and secreted form. Their use could condition the inhibitory environment for homophilic L1-enhanced axon regrowth not only in spinal cord regeneration, but also in other lesion paradigms.