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  Embryonic stem cell-derived neural progenitors as non-tumorigenic source for dopaminergic neurons.

Liao, M. C., Diaconu, M., Monecke, S., Collombat, P., Timaeus, C., Kuhlmann, T., et al. (2014). Embryonic stem cell-derived neural progenitors as non-tumorigenic source for dopaminergic neurons. World Journal of Stem Cells, 6(2), 248-255. doi:10.4252/wjsc.v6.i2.248.

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Item Permalink: http://hdl.handle.net/11858/00-001M-0000-0027-AD85-D Version Permalink: http://hdl.handle.net/11858/00-001M-0000-0027-CEE0-9
Genre: Journal Article

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 Creators:
Liao, M. C.1, Author              
Diaconu, M.1, Author              
Monecke, Sebastian, Author
Collombat, Patrick, Author
Timaeus, Charles, Author
Kuhlmann, Tanja, Author
Paulus, Walter, Author
Trenkwalder, Claudia, Author
Dressel, Ralf, Author
Mansouri, A.1, Author              
Affiliations:
1Research Group of Molecular Cell Differentiation, MPI for Biophysical Chemistry, Max Planck Society, ou_578588              

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Free keywords: Human embryonic stem cells, Neural progenitor cells, Teratoma, Pluripotency, Dopaminergic neurons
 Abstract: AIM: To find a safe source for dopaminergic neurons, we generated neural progenitor cell lines from human embryonic stem cells. METHODS: The human embryonic stem (hES) cell line H9 was used to generate human neural progenitor (HNP) cell lines. The resulting HNP cell lines were differentiated into dopaminergic neurons and analyzed by quantitative real-time polymerase chain reaction and immunofluorescence for the expression of neuronal differentiation markers, including beta-III tubulin (TUJ1) and tyrosine hydroxylase (TH). To assess the risk of teratoma or other tumor formation, HNP cell lines and mouse neuronal progenitor (MNP) cell lines were injected subcutaneously into immunodeficient SCID/beige mice. RESULTS: We developed a fairly simple and fast protocol to obtain HNP cell lines from hES cells. These cell lines, which can be stored in liquid nitrogen for several years, have the potential to differentiate in vitro into dopaminergic neurons. Following day 30 of differentiation culture, the majority of the cells analyzed expressed the neuronal marker TUJ1 and a high proportion of these cells were positive for TH, indicating differentiation into dopaminergic neurons. In contrast to H9 ES cells, the HNP cell lines did not form tumors in immunodeficient SCID/beige mice within 6 mo after subcutaneous injection. Similarly, no tumors developed after injection of MNP cells. Notably, mouse ES cells or neuronal cells directly differentiated from mouse ES cells formed teratomas in more than 90% of the recipients. CONCLUSION: Our findings indicate that neural progenitor cell lines can differentiate into dopaminergic neurons and bear no risk of generating teratomas or other tumors in immunodeficient mice.

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Language(s): eng - English
 Dates: 2014-04-26
 Publication Status: Published online
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 Rev. Method: Peer
 Identifiers: DOI: 10.4252/wjsc.v6.i2.248
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Title: World Journal of Stem Cells
Source Genre: Journal
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Pages: - Volume / Issue: 6 (2) Sequence Number: - Start / End Page: 248 - 255 Identifier: -