title: Altered differentiation of CNS neural progenitor cells after transplantation into the injured adult rat spinal cord.
abstract: Denervation of CNS neurons and peripheral organs is a consequence of traumatic SCI. Intraspinal transplantation of embryonic CNS neurons is a potential strategy for reinnervating these targets. Neural progenitor cell lines are being investigated as alternates to embryonic CNS neurons. RN33B is an immortalized neural progenitor cell line derived from embryonic rat raphe nuclei following infection with a retrovirus encoding the temperature-sensitive mutant of SV40 large T-antigen. Transplantation studies have shown that local epigenetic signals in intact or partially neuron-depleted adult rat hippocampal formation or striatum direct RN33B cell differentiation to complex multipolar morphologies resembling endogenous neurons. After transplantation into neuron-depleted regions of the hippocampal formation or striatum, RN33B cells were relatively undifferentiated or differentiated with bipolar morphologies. The present study examines RN33B cell differentiation after transplantation into normal spinal cord and under different lesion conditions. Adult rats underwent either unilateral lesion of lumbar spinal neurons by intraspinal injection of kainic acid or complete transection at the T10 spinal segment. Neonatal rats underwent either unilateral lesion of lumbar motoneurons by sciatic nerve crush or complete transection at the T10 segment. At 2 or 6-7 wk postinjury, lacZ-labeled RN33B cells were transplanted into the lumbar enlargement of injured and age-matched normal rats. At 2 wk posttransplantation, bipolar and some multipolar RN33B cells were found throughout normal rat gray matter. In contrast, only bipolar RN33B cells were seen in gray matter of kainic acid lesioned, sciatic nerve crush, or transection rats. These observations suggest that RN33B cell multipolar morphological differentiation in normal adult spinal cord is mediated by direct cell-cell interaction through surface molecules on endogenous neurons and may be suppressed by molecules released after SCI. They also indicate that the fate of immortalized neural progenitor cell lines in injured CNS must be stringently characterized.
authors.affiliation: The Miami Project to Cure Paralysis, University of Miami School of Medicine, FL 33136, USA.
authors.forename: S M
authors.initials: SM
authors.lastname: Onifer
authors.forename: A B
authors.initials: AB
authors.lastname: Cannon
authors.forename: S R
authors.initials: SR
authors.lastname: Whittemore
mesh_terms: D000818:Animals; D001973:Bromodeoxyuridine; D002454:Cell Differentiation / Q000502:physiology; D002461:Cell Line, Transformed / Q000737:chemistry / Q000637:transplantation; D002795:Choline O-Acetyltransferase / Q000032:analysis / Q000235:genetics; D003714:Denervation; D018690:Excitatory Amino Acid Agonists; D005260:Female; D007381:Intermediate Filament Proteins / Q000032:analysis / Q000235:genetics; D007608:Kainic Acid; D007763:Lac Operon; D008297:Male; D009409:Nerve Crush; D009419:Nerve Tissue Proteins; D064231:Nestin; D009474:Neurons / Q000166:cytology / Q000201:enzymology / Q000637:transplantation*; D009498:Neurotoxins; D010641:Phenotype; D051381:Rats; D017207:Rats, Sprague-Dawley; D012584:Sciatic Nerve / Q000601:surgery; D013116:Spinal Cord / Q000601:surgery*; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000737:chemistry / Q000166:cytology
chemical_list: D018690:Excitatory Amino Acid Agonists; D007381:Intermediate Filament Proteins; D009419:Nerve Tissue Proteins; C577486:Nes protein, rat; D064231:Nestin; D009498:Neurotoxins; D002795:Choline O-Acetyltransferase; D001973:Bromodeoxyuridine; D007608:Kainic Acid