RGD Reference Report - TrkC overexpression enhances survival and migration of neural stem cell transplants in the rat spinal cord. - Rat Genome Database

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TrkC overexpression enhances survival and migration of neural stem cell transplants in the rat spinal cord.

Authors: Castellanos, DA  Tsoulfas, P  Frydel, BR  Gajavelli, S  Bes, JC  Sagen, J 
Citation: Castellanos DA, etal., Cell Transplant. 2002;11(3):297-307.
RGD ID: 2325633
Pubmed: PMID:12075995   (View Abstract at PubMed)

Although CNS axons have the capacity to regenerate after spinal cord injury when provided with a permissive substrate, the lack of appropriate synaptic target sites for regenerating fibers may limit restoration of spinal circuitry. Studies in our laboratory are focused on utilizing neural stem cells to provide new synaptic target sites for regenerating spinal axons following injury. As an initial step, rat neural precursor cells genetically engineered to overexpress the tyrosine kinase C (trkC) neurotrophin receptor were transplanted into the intact rat spinal cord to evaluate their survival and differentiation. Cells were either pretreated in vitro prior to transplantation with trkC ligand neurotrophin-3 (NT-3) to initiate differentiation or exposed to NT-3 in vivo following transplantation via gelfoam or Oxycel. Both treatments enhanced survival of trkC-overexpressing stem cells to nearly 100%, in comparison with approximately 30-50% when either NT-3 or trkC was omitted. In addition, increased migration of trkC-overexpressing cells throughout the spinal gray matter was noted, particularly following in vivo NT-3 exposure. The combined trkC expression and NT-3 treatment appeared to reduce astrocytic differentiation of transplanted neural precursors. Decreased cavitation and increased beta-tubulin fibers were noted in the vicinity of transplanted cells, although the majority of transplanted cells appeared to remain in an undifferentiated state. These findings suggest that genetically engineered neural stem cells in combination with neurotrophin treatment may be a useful addition to strategies for repair of spinal neurocircuitry following injury.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Ntrk3Ratnegative regulation of astrocyte differentiation  IMP  RGD 
Ntrk3Ratneuron migration  IMP  RGD 
Ntrk3Ratregulation of neural precursor cell proliferation  IMP  RGD 

Objects Annotated

Genes (Rattus norvegicus)
Ntrk3  (neurotrophic receptor tyrosine kinase 3)

Additional Information