Neurons derived from human mesenchymal stem cells show synaptic transmission and can be induced to produce the neurotransmitter substance P by interleukin-1 alpha

Stem Cells. 2005 Mar;23(3):383-91. doi: 10.1634/stemcells.2004-0251.

Abstract

Mesenchymal stem cells (MSCs) exhibit immune-suppressive properties, follow a pattern of multilineage differentiation, and exhibit transdifferentiation potential. Ease in expansion from adult bone marrow, as well as its separation from ethical issues, makes MSCs appealing for clinical application. MSCs treated with retinoic acid resulted in synaptic transmission, based on immunostaining of synaptophysin and electrophysiological studies. In situ hybridization indicated that the neurotransmitter gene preprotachykinin-I was expressed in these cells. However, translation of this gene only occurred after stimulation with interleukin (IL)-1 alpha. This effect was blunted by costimulation with IL-1 receptor antagonist. This study reports on the ability of MSCs to be transdifferentiated into neurons with functional synapses with the potential to become polarized towards producing specific neurotransmitters.

Publication types

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

MeSH terms

  • Bone Marrow Cells / cytology
  • Cell Differentiation / drug effects*
  • Electrophysiology
  • Gene Expression / drug effects
  • Humans
  • Immunohistochemistry
  • In Situ Hybridization
  • Interleukin 1 Receptor Antagonist Protein
  • Interleukin-1 / pharmacology*
  • Intermediate Filament Proteins / metabolism
  • Mesenchymal Stem Cells / cytology*
  • Mesenchymal Stem Cells / drug effects
  • Mesenchymal Stem Cells / metabolism
  • Microtubule-Associated Proteins / metabolism
  • Nerve Tissue Proteins / metabolism
  • Nestin
  • Neurofilament Proteins / metabolism
  • Neurons / cytology
  • Neurons / metabolism
  • Neurons / physiology*
  • Protein Precursors / genetics
  • Sialoglycoproteins / pharmacology
  • Substance P / metabolism*
  • Synaptic Transmission / physiology*
  • Synaptophysin / metabolism
  • Tachykinins / genetics
  • Tretinoin / pharmacology

Substances

  • IL1RN protein, human
  • Interleukin 1 Receptor Antagonist Protein
  • Interleukin-1
  • Intermediate Filament Proteins
  • MAP2 protein, human
  • Microtubule-Associated Proteins
  • NES protein, human
  • Nerve Tissue Proteins
  • Nestin
  • Neurofilament Proteins
  • Protein Precursors
  • Sialoglycoproteins
  • Synaptophysin
  • Tachykinins
  • preprotachykinin
  • Substance P
  • Tretinoin