Implantation of c-mycER TAM immortalized human mesencephalic-derived clonal cell lines ameliorates behavior dysfunction in a rat model of Parkinson's disease

Stem Cells Dev. 2009 Mar;18(2):307-19. doi: 10.1089/scd.2008.0078.


Human neural stem cells offer the hope that a cell therapy treatment for Parkinson's disease (PD) could be made widely available. In this study, we describe two clonal human neural cell lines, derived from two different 10-week-old fetal mesencephalic tissues and immortalized with the c-mycER(TAM) transgene. Under the growth control of 4-hydroxytamoxifen, both cell lines display stable long-term growth in culture with a normal karyotype. In vitro, these nestin-positive cells are able to differentiate into tyrosine hydroxylase (TH)-positive neurons and are multipotential. Implantation of the undifferentiated cells into the 6-OHDA substantia nigral lesioned rat model displayed sustained improvements in a number of behavioral tests compared with noncell-implanted, vehicle-injected controls over the course of 6 months. Histological analysis of the brains showed survival of the implanted cells but no evidence of differentiation into TH-positive neurons. An average increase of approximately 26% in host TH immunoreactivity in the lesioned dorsal striatum was observed in the cell-treated groups compared to controls, with no difference in loss of TH cell bodies in the lesioned substantia nigra. Further analysis of the cell lines identified a number of expressed trophic factors, providing a plausible explanation for the effects observed in vivo. The exact mechanisms by which the implanted human neural cell lines provide behavioral improvements in the PD model are not completely understood; however, these findings provide evidence that cell therapy can be a potent treatment for PD acting through a mechanism independent of dopaminergic neuronal cell replacement.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Behavior, Animal / physiology*
  • Brain / enzymology
  • Brain / pathology
  • Cell Differentiation
  • Cell Line, Transformed
  • Cell Survival
  • Clone Cells
  • Disease Models, Animal
  • Humans
  • Intercellular Signaling Peptides and Proteins / pharmacology
  • Mesencephalon / transplantation*
  • Neurons / cytology
  • Parkinson Disease / physiopathology*
  • Parkinson Disease / therapy*
  • Prosthesis Implantation*
  • Proto-Oncogene Proteins c-myc / metabolism*
  • Rats
  • Rotarod Performance Test
  • Tamoxifen / metabolism*
  • Tyrosine 3-Monooxygenase / metabolism


  • Intercellular Signaling Peptides and Proteins
  • Proto-Oncogene Proteins c-myc
  • Tamoxifen
  • Tyrosine 3-Monooxygenase