Neuronal Differentiation of Adult Rat Hippocampus-Derived Neural Stem Cells Transplanted Into Embryonic Rat Explanted Retinas With Retinoic Acid Pretreatment

Brain Res. 2002 Nov 8;954(2):286-93. doi: 10.1016/s0006-8993(02)03356-5.


The purpose of this study was to evaluate the effects of the retinal environment and retinoic acid (RA) pretreatment on the differentiation of transplanted adult rat hippocampus-derived neural stem cells (AHSCs). AHSCs were transplanted into embryonic (E18) or neonatal (P6) rat retinal explants and the mixture was cultured for 2 weeks. Other AHSCs were stimulated by 0.5 microM all-trans RA for 6 days before transplantation. Immunofluorescent double staining showed that a larger number of AHSCs became beta-tubulin III-positive neurons in the E18 than in P6 retinas. In addition, many AHSCs became MAP2ab-positive and MAP5-positive neurons following RA pretreatment and transplantation. Only a few AHSCs became HPC-1-, calbindin-, PKC- or rhodopsin-positive cells under these conditions. We conclude that the microenvironment supplied by embryonic retinas is conductive to neuronal differentiation in general. RA stimulation before transplantation was also effective in stimulating differentiation.

MeSH terms

  • Animals
  • Calbindins
  • Cell Culture Techniques
  • Cell Differentiation / drug effects
  • Glial Fibrillary Acidic Protein / metabolism
  • Hippocampus / transplantation*
  • Immunohistochemistry
  • Intermediate Filament Proteins / metabolism
  • Keratolytic Agents / pharmacology*
  • Microtubule-Associated Proteins / metabolism
  • Nerve Tissue Proteins*
  • Nestin
  • Neurons / transplantation*
  • Protein Kinase C / metabolism
  • Rats
  • Rats, Inbred F344
  • Retina / metabolism*
  • Rhodopsin / metabolism
  • S100 Calcium Binding Protein G / metabolism
  • Stem Cell Transplantation*
  • Stem Cells / chemistry
  • Stem Cells / drug effects
  • Stem Cells / metabolism*
  • Tretinoin / pharmacology*
  • Tubulin / metabolism


  • Calbindins
  • Glial Fibrillary Acidic Protein
  • Intermediate Filament Proteins
  • Keratolytic Agents
  • Microtubule-Associated Proteins
  • Nerve Tissue Proteins
  • Nes protein, rat
  • Nestin
  • S100 Calcium Binding Protein G
  • Tubulin
  • Tretinoin
  • Rhodopsin
  • Protein Kinase C