Sensory neuron differentiation potential of in utero mesenchymal stem cell transplantation in rat fetuses with spina bifida aperta

Birth Defects Res A Clin Mol Teratol. 2015 Sep;103(9):772-9. doi: 10.1002/bdra.23401. Epub 2015 Jul 14.


Background: In previous studies, we found that the deficiency of sensory and motor neurons was a primary defect associated with the spinal malformation. Upon prenatal treatment of spina bifida through in utero stem cell transplantation in a retinoic acid-induced spina bifida rat model, we found that the mesenchymal stem cell (MSCs) survived, migrated, and differentiated into cells of a neural lineage. In the present study, we investigated whether the transplanted MSCs had the potential to differentiate into sensory neurons or to protect sensory neurons in the defective spinal cord.

Methods: Pregnant rats treated with retinoic acid on embryonic day (E) 10, underwent fetal surgery for MSC transplantation on E16. The fetuses were harvested on E20. Immunofluorescence was used to detect the expression of Brn3a protein in the transplanted MSCs and dorsal root ganglion (DRG) neurons in the defective spinal cords. The expression of the transcription factors Brn3a and Runx1 in spinal cords was analyzed using real-time polymerase chain reaction.

Results: Some of the transplanted MSCs expressed sensory neuron cell specific phenotypes. The expression of Brn3a and Runx1 was upregulated in the defective spinal cords when compared to controls. The percentage of Brn3a-positive neurons in DRG was also increased after transplantation.

Conclusion: Our results indicate that the transplantation of MSCs into the spinal cord could promote the transplanted MSCs and the surrounding cells to differentiate toward a sensory neuron cell fate and to play an important role in protecting sensory neurons in DRG. This approach might be of value in the treatment of sensory neuron deficiency in spina bifida aperta.

Keywords: in utero MSCs transplantation; mesenchymal stem cell; neural tube defects; prenatal treatment; sensory neuron regeneration.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Apoptosis / physiology
  • Cell Differentiation / drug effects
  • Cell Differentiation / physiology*
  • Female
  • Fetus / drug effects
  • Fetus / physiopathology*
  • Ganglia, Spinal / drug effects
  • Ganglia, Spinal / physiopathology
  • Humans
  • Mesenchymal Stem Cell Transplantation / methods
  • Mesenchymal Stem Cells / drug effects
  • Mesenchymal Stem Cells / physiology*
  • Pregnancy
  • Rats
  • Sensory Receptor Cells / drug effects
  • Sensory Receptor Cells / physiology*
  • Spina Bifida Cystica / physiopathology*
  • Spinal Cord / drug effects
  • Spinal Cord / physiopathology
  • Tretinoin / pharmacology
  • Up-Regulation / drug effects
  • Up-Regulation / physiology


  • Tretinoin