Astrocytes enhance long-term survival of cholinergic neurons differentiated from human fetal neural stem cells

Paivi M. Jordan, Lisa D. Cain, Ping Wu

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Establishment of an in vitro model of human cholinergic neurons would be highly desirable for understanding and developing treatment for Alzheimer's and motoneuron diseases. Previously we reported that the combination of basic fibroblast growth factor (bFGF), heparin, and laminin directs human fetal neural stem cells to form cholinergic neurons. One problem, however, is that long-term in vitro survival of these cells is low. Our goal for this study was to determine whether astrocytes or their secreted factors enhance differentiation and survival of cholinergic neurons under long-term differentiation conditions. We demonstrate here that astrocytes or astrocyte conditioned media did not enhance cholinergic differentiation but did increase the long-term survival of differentiated human neural stem cells, particularly cholinergic neurons. We further show that astrocytes protected long-term-differentiated cells from apoptotic cell death, which is at least partially mediated by astrocyte-secreted bFGF. Our findings indicate that long-term survival of human stem cell-derived cholinergic neurons requires trophic factors from nonneuronal cells. This data may provide insights into the development of an in vitro model of long-term cultured human cholinergic neurons useful for understanding of the mechanisms of cholinergic differentiation and developing treatments for neurological diseases.

Original languageEnglish (US)
Pages (from-to)35-47
Number of pages13
JournalJournal of Neuroscience Research
Volume86
Issue number1
DOIs
StatePublished - Jan 2008

Fingerprint

Fetal Stem Cells
Cholinergic Neurons
Neural Stem Cells
Astrocytes
Fibroblast Growth Factor 2
Cholinergic Agents
Motor Neurons
Laminin
Conditioned Culture Medium
Heparin
Cell Survival
Alzheimer Disease
Cell Death
Stem Cells
Survival

Keywords

  • Astrocytes
  • bFGF
  • Cell survival
  • Cholinergic neurons
  • Coculture
  • Human neural stem cells

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Astrocytes enhance long-term survival of cholinergic neurons differentiated from human fetal neural stem cells. / Jordan, Paivi M.; Cain, Lisa D.; Wu, Ping.

In: Journal of Neuroscience Research, Vol. 86, No. 1, 01.2008, p. 35-47.

Research output: Contribution to journalArticle

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