Neurobiology of human neurons (NT2N) grafted into mouse spinal cord: implications for improving therapy of spinal cord injury.
Emerging data suggest that current strategies for the treatment of spinal cord injury might be improved or augmented by spinal cord grafts of neural cells, and it is possible that grafted neurons might have therapeutic potential. Thus, here we have summarized recent studies of the neurobiology of clonal human (NT2N) neurons grafted into spinal cord of immunodeficient athymic nude mice. Postmitotic human NT2N neurons derived in vitro from an embryonal carcinoma cell line (NT2) were transplanted into spinal cord of neonatal, adolescent and adult nude mice where they became integrated into the host gray and white matter, did not migrate from the graft site, and survived for > 15 months after implantation. The neuronal phenotype of the grafted NT2N cells was similar in gray and white matter regardless of host age at implantation, and some of the processes extended by the transplanted NT2N neurons became ensheathed by oligodendrocytes. However, there were consistent differences between NT2N processes traversing white versus gray matter. Most notably, NT2N processes with a trajectory in white matter extended over much longer distances (some for > 2 cm) than those confined to gray matter. Thus, NT2N neurons grafted into spinal cord of nude mice integrated into gray as well as white matter, where they exhibited and maintained the morphological and molecular phenotype of mature neurons for > 15 months after implantation. Also, the processes extended by grafted NT2N neurons differentially responded to cues restricted to gray versus white matter. Further insight into the neurobiology of grafted human NT2N neurons in the normal and injured spinal cord of experimental animals may lead to novel and more effective strategies for the treatment of spinal cord injury.
Lee
V M
VM
Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Hospital of the University of Pennsylvania, Philadelphia 19104-4283, USA. vmylee@mail.med.vpenn.edu
Hartley
R S
RS
Trojanowski
J Q
JQ
D000818:Animals; D015415:Biomarkers / Q000032:analysis; D002454:Cell Differentiation / Q000502:physiology; D054278:Embryonal Carcinoma Stem Cells; D016332:Fetal Tissue Transplantation / Q000379:methods* / Q000639:trends*; D006801:Humans; D016867:Immunocompromised Host / Q000502:physiology; D051379:Mice; D008819:Mice, Nude / Q000033:anatomy & histology / Q000276:immunology / Q000601:surgery; D014411:Neoplastic Stem Cells / Q000166:cytology / Q000276:immunology / Q000637:transplantation*; D009474:Neurons / Q000166:cytology / Q000276:immunology / Q000637:transplantation*; D010641:Phenotype; D013116:Spinal Cord / Q000166:cytology / Q000378:metabolism / Q000601:surgery*; D013119:Spinal Cord Injuries / Q000601:surgery*
D015415:Biomarkers