Is Tauroursodeoxycholic Acid Effective in Redirecting Stem Cells For Neural Differentiation?
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1
University of Lisbon, iMed.UL- Faculty of Pharmacy, Poland
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2
University of Lisbon, IMM, Portugal
The poor survival and differentiation of stem cells after transplantation has been a major problem of stem cell therapy, urging for a better understanding of the molecular mechanisms underlying these processes. We have previously shown that the endogenous bile acid tauroursodeoxycholic acid (TUDCA) is an inhibitor of apoptosis. TUDCA is neuroprotective in animal models of acute stroke and Huntington’s disease and improves survival and function of cell transplants in Parkinson’s disease. Finally, it has been shown that apoptosis-related proteins are pivotal for differentiation, targeting molecules different from those associated with cell death. We aimed to address the role of TUDCA in differentiation of embryonic stem cell (ESC)- derived neural progenitor cells (NPC). 46C, a Sox1-GFP mouse ESC line, was used as an in vitro model of neurogenesis. After induction of monolayer differentiation into NPC, cells were treated with TUDCA or with a gamma-secretase inhibitor (LY411575) as positive control for neural differentiation. RT-PCR data showed that TUDCA increases the expression of both proliferation and differentiation-associated markers, such as Hes6, Sox3 and Ngn2. Proliferation and cell death measurements indicated that TUDCA treatment increases stem cell survival throughout differentiation, when compared with LY411575. Future work includes further characterization of the TUDCA pro-neural differentiation function. This study exploits the potential use of TUDCA as a modulator of the long term-survival and differentiation of neural stem cells, contributing to a more efficient use of stem cells in neural-replacement therapy. (Supported by FEDER and FCT, PTDC/BIA- BCM/67922/2006 and SFRH/BD/42008/2007).
Conference:
11th Meeting of the Portuguese Society for Neuroscience, Braga, Portugal, 4 Jun - 6 Jun, 2009.
Presentation Type:
Poster Presentation
Topic:
Abstracts
Citation:
Santos
DM,
Sola
S,
Abranches
E,
Henrique
D and
Rodrigues
CM
(2009). Is Tauroursodeoxycholic Acid Effective in Redirecting Stem Cells For Neural Differentiation?.
Front. Neurosci.
Conference Abstract:
11th Meeting of the Portuguese Society for Neuroscience.
doi: 10.3389/conf.neuro.01.2009.11.102
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Received:
10 Aug 2009;
Published Online:
10 Aug 2009.
*
Correspondence:
Daniela M Santos, University of Lisbon, iMed.UL- Faculty of Pharmacy, Lisbon, Poland, susana.sola@ff.ul.pt