Neuroprotective effect of adult hematopoietic stem cells in a mouse model of motoneuron degeneration

Neurobiol Dis. 2007 May;26(2):408-18. doi: 10.1016/j.nbd.2007.01.008. Epub 2007 Feb 6.

Abstract

Degenerative spinal motor diseases, like amyotrophic lateral sclerosis, are produced by progressive degeneration of motoneurons. Their clinical manifestations include a progressive muscular weakness and atrophy, which lead to paralysis and premature death. Current pharmacological therapies fail to stop the progression of motor deficits or to restore motor function. The purpose of our study was to explore the possible beneficial effect of mouse adult hematopoietic stem cells (hSCs) transplanted into the spinal cord of a mouse model of motoneuron degeneration. Our results show that grafted hSCs survive in the spinal cord. In addition, the number of motoneurons in the transplanted spinal cord is larger than in non-transplanted mdf mice at the same spinal cord segments and importantly, motor function significantly improves. These effects can be explained by the increased levels of glial cell line derived neurotrophic factor (GDNF) around host motoneurons produced by the grafted cells. Thus, these experiments demonstrate the neuroprotective effect of adult hSCs in the model employed and indicate that this cell type may contribute to ameliorating motor function in degenerative spinal motor diseases.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Action Potentials / physiology
  • Animals
  • Cell Count
  • Cell Differentiation / physiology*
  • Cell Lineage / physiology
  • Cytoprotection / physiology
  • Disease Models, Animal
  • Glial Cell Line-Derived Neurotrophic Factor / metabolism
  • Graft Survival / physiology*
  • Hematopoietic Stem Cells / metabolism*
  • Mice
  • Mice, Neurologic Mutants
  • Motor Neuron Disease / metabolism
  • Motor Neuron Disease / physiopathology
  • Motor Neuron Disease / therapy*
  • Motor Neurons / physiology
  • Muscle, Skeletal / innervation
  • Muscle, Skeletal / physiology
  • Recovery of Function / physiology
  • Spinal Cord / physiopathology
  • Spinal Cord / surgery*
  • Stem Cell Transplantation / methods*

Substances

  • Glial Cell Line-Derived Neurotrophic Factor