Steroid-mediated differentiation of neural/neuronal cells from epithelial ovarian precursors in vitro

Antonin Bukovsky, Michael Caudle, Marta Svetlikova

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

We reported earlier that occasional neurons evolve in human cultures of pluripotent ovarian epithelial stem cells. In subsequent experiments, frequent transdifferentiation into neural stem cells (NSC) and differentiating neurons was observed in human ovarian epithelial stem cells and porcine granulosa cells after exposure to certain combinations of sex steroids. Testosterone (TS), progesterone (PG) or estradiol (E2) alone do not increase the emergence of neurons. However, a mixture of TS + PG after E2 pretreatment converted a majority of ovarian epithelial stem cells or porcine granulosa cells into NSC and differentiating neuronal cells within one to three hours. Cultured neurons manifested an interconnectivity resembling primitive neuronal pathways in culture. These converted cells expressed the cell markers SSEA-1, SSEA-4, NCAM and Thy-1 glycoconjugates of NSC and neurons, and differentiating cells showed characteristic neuronal morphology. Emergence of NSC and neuronal cells was associated with significant cellular depletion of L-glutamic acid (glutamate), which serves as the major excitatory neurotransmitter in the vertebrate CNS and its fast removal is essential for preventing glutamate excitotoxicity. These observations suggest that certain sequential systemic treatment with common sex steroids and their mixture might be effective in the treatment or prevention of degenerative CNS disorders. The ovarian stem cell cultures readily obtainable from human ovaries regardless of the woman's age have the potential to produce NSC for autologous regenerative treatment of neurologic diseases in aging women. Finally, the proper combination of sex steroids could possibly be employed for transdifferentiation of adult bone marrow stem cells or mobilized peripheral blood cells into autologous NSC and stimulate their neuronal differentiation after homing in the CNS.

Original languageEnglish (US)
Pages (from-to)3577-3583
Number of pages7
JournalCell Cycle
Volume7
Issue number22
DOIs
StatePublished - Nov 15 2008
Externally publishedYes

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Neural Stem Cells
Epithelial Cells
Steroids
Stem Cells
Neurons
Glutamic Acid
Granulosa Cells
Progesterone
Testosterone
Swine
CD15 Antigens
Neural Cell Adhesion Molecules
Glycoconjugates
Nervous System Diseases
Bone Marrow Cells
Neurotransmitter Agents
Vertebrates
In Vitro Techniques
Ovary
Estradiol

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Developmental Biology
  • Cell Biology

Cite this

Steroid-mediated differentiation of neural/neuronal cells from epithelial ovarian precursors in vitro. / Bukovsky, Antonin; Caudle, Michael; Svetlikova, Marta.

In: Cell Cycle, Vol. 7, No. 22, 15.11.2008, p. 3577-3583.

Research output: Contribution to journalArticle

Bukovsky, Antonin ; Caudle, Michael ; Svetlikova, Marta. / Steroid-mediated differentiation of neural/neuronal cells from epithelial ovarian precursors in vitro. In: Cell Cycle. 2008 ; Vol. 7, No. 22. pp. 3577-3583.
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