Neuroectodermal differentiation from mouse multipotent adult progenitor cells

Proc Natl Acad Sci U S A. 2003 Sep 30;100 Suppl 1(Suppl 1):11854-60. doi: 10.1073/pnas.1834196100. Epub 2003 Aug 18.

Abstract

We recently showed that a rare cell from murine bone marrow, which we termed multipotent adult progenitor cells (MAPCs), can be expanded for >120 population doublings. Mouse (m)MAPCs differentiate into mesenchymal lineage cells as well as endothelium and endoderm, and, when injected in the blastocyst, mMAPCs contribute to most if not all somatic cell lineages including the different cell types of the brain. Our results, reported herein, demonstrate that mMAPCs can also be induced to differentiate into cells having anatomical and electrophysiological characteristics similar to those of midbrain neurons. Differentiation to a neuronal phenotype was achieved by coculturing mMAPCs with astrocytes, suggesting that neuronal differentiation may require astrocyte-derived factors similar to what is required for the differentiation of embryonic stem cells and neural stem cells to neurons. Differentiation of mMAPCs to neuron-like cells follows similar developmental steps as described for embryonic stem cells and neural stem cells. MAPCs therefore may constitute a source of cells for treatment of central nervous system disorders.

Publication types

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

MeSH terms

  • Animals
  • Astrocytes / cytology
  • Astrocytes / metabolism
  • Base Sequence
  • Cell Differentiation
  • Cells, Cultured
  • Coculture Techniques
  • Culture Media, Conditioned
  • DNA, Complementary / genetics
  • Dopamine / metabolism
  • Ectoderm / cytology
  • Ectoderm / metabolism
  • Hematopoietic Stem Cells / cytology*
  • Hematopoietic Stem Cells / metabolism
  • Mice
  • Neurons / cytology
  • Neurons / metabolism
  • Phenotype
  • Pluripotent Stem Cells / cytology*
  • Pluripotent Stem Cells / metabolism
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Serotonin / metabolism
  • Sodium Channels / metabolism
  • gamma-Aminobutyric Acid / metabolism

Substances

  • Culture Media, Conditioned
  • DNA, Complementary
  • RNA, Messenger
  • Sodium Channels
  • Serotonin
  • gamma-Aminobutyric Acid
  • Dopamine