Increased neuronal proliferation in the dentate gyrus of aged rats following neural stem cell implantation

Dong Hyuk Park, David J. Eve, Paul R. Sanberg, James Musso, Adam D. Bachstetter, Alan Wolfson, Andrea Schlunk, Marc Olivier Baradez, John D. Sinden, Carmelina Gemma

Research output: Contribution to journalArticlepeer-review

46 Scopus citations


It is now well accepted that the brain is able to generate newborn neurons from a population of resident multipotential neural stem cells (NSCs) located in two discrete regions of the brain. The capacity for neurogenesis appears to diminish over the lifespan of an organism. Methods to potentiate the proliferation of new neuronal or glial cells within the central nervous system from resident NSCs could have therapeutic potential following an insult, such as stroke, or to replace lost cells as a result of a neurodegenerative disease. We implanted cells from a human NSC cell line, CTX0E03, originally derived from fetal cortical tissue directly into the ventricles of aged rats. CTX0E03 cells have angiogenic properties via secretion of growth factors, so we investigated if the implanted cells would stimulate proliferation of NSCs within the subgranular zone (SGZ) of the dentate gyrus. Bromodeoxyuridine staining demonstrated significantly increased proliferation in the SGZ. Absence of double labeling for human nuclear antigen suggested that the increased proliferation was from endogenous neural progenitor cells. The acute treatment also led to an increased number of immature neurons as demonstrated by immunohistochemical staining for the immature neuronal marker doublecortin. The data suggest that implants of exogenous NSCs may promote regeneration in aging organisms through stimulation of endogenous neurogenesis.

Original languageEnglish
Pages (from-to)175-180
Number of pages6
JournalStem Cells and Development
Issue number2
StatePublished - Feb 1 2010

ASJC Scopus subject areas

  • Hematology
  • Developmental Biology
  • Cell Biology


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