Human neural progenitor cells over-expressing IGF-1 protect dopamine neurons and restore function in a rat model of Parkinson's disease

Exp Neurol. 2008 Jan;209(1):213-23. doi: 10.1016/j.expneurol.2007.09.022. Epub 2007 Oct 4.

Abstract

Growth factors such as glial cell line-derived neurotrophic factor (GDNF) have been shown to prevent neurodegeneration and promote regeneration in many animal models of Parkinson's disease (PD). Insulin-like growth factor 1 (IGF-1) is also known to have neuroprotective effects in a number of disease models but has not been extensively studied in models of PD. We produced human neural progenitor cells (hNPC) releasing either GDNF or IGF-1 and transplanted them into a rat model of PD. hNPC secreting either GDNF or IGF-1 were shown to significantly reduce amphetamine-induced rotational asymmetry and dopamine neuron loss when transplanted 7 days after a 6-hydroxydopamine (6-OHDA) lesion. Neither untransduced hNPC nor a sham transplant had this effect suggesting GDNF and IGF-1 release was required. Interestingly, GDNF, but not IGF-1, was able to protect or regenerate tyrosine hydroxylase-positive fibers in the striatum. In contrast, IGF-1, but not GDNF, significantly increased the overall survival of hNPC both in vitro and following transplantation. This suggests a dual role of IGF-1 to both increase hNPC survival after transplantation and exert trophic effects on degenerating dopamine neurons in this rat model of PD.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Amphetamine / pharmacology
  • Animals
  • Cell Differentiation / drug effects
  • Cells, Cultured
  • Central Nervous System Stimulants / pharmacology
  • Data Interpretation, Statistical
  • Dopamine / physiology*
  • Enzyme-Linked Immunosorbent Assay
  • Glial Cell Line-Derived Neurotrophic Factor / pharmacology
  • Humans
  • Immunohistochemistry
  • Insulin-Like Growth Factor I / biosynthesis*
  • Insulin-Like Growth Factor I / pharmacology
  • Lentivirus / genetics
  • Male
  • Nerve Fibers / enzymology
  • Neurons / metabolism*
  • Neurons / pathology*
  • Oxidopamine
  • Parkinson Disease, Secondary / chemically induced
  • Parkinson Disease, Secondary / pathology
  • Parkinson Disease, Secondary / therapy*
  • Rats
  • Rats, Inbred Lew
  • Stem Cell Transplantation*
  • Stem Cells / metabolism*
  • Stereotyped Behavior / drug effects
  • Sympatholytics
  • Tyrosine 3-Monooxygenase / metabolism

Substances

  • Central Nervous System Stimulants
  • Glial Cell Line-Derived Neurotrophic Factor
  • Sympatholytics
  • Insulin-Like Growth Factor I
  • Oxidopamine
  • Amphetamine
  • Tyrosine 3-Monooxygenase
  • Dopamine