Incorporation of retinoic acid releasing microspheres into pluripotent stem cell aggregates for inducing neuronal differentiation

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dc.contributor.author Gomez, Jose Carlos
dc.contributor.author Edgar, John M
dc.contributor.author Agbay, Andrew M
dc.contributor.author Bibault, Emma
dc.contributor.author Montgomery, Amy
dc.contributor.author Mohtaram, Nima Khadem
dc.contributor.author Willerth, Stephanie
dc.date.accessioned 2015-06-15T23:11:32Z
dc.date.available 2016-06-05T11:22:06Z
dc.date.copyright 2015 en_US
dc.date.issued 2015
dc.identifier.citation Gomez et al. Incorporation of retinoic acid releasing microspheres into aggregates of pluripotent stem cells for inducing neuronal differentiation. In press at Cellular and Molecular Bioengineering. en_US
dc.identifier.uri http://link.springer.com/article/10.1007/s12195-015-0401-z
dc.identifier.uri http://hdl.handle.net/1828/6263
dc.description.abstract Pluripotent stem cells (PSCs) can form any specialized cell type found in the body making them an excellent tool for regenerative medicine applications. Directed differentiation of PSCs into specific phenotypes can be accomplished by introducing specific chemical cues such as the small molecule retinoic acid (RA). Expressed in the developing nervous system, RA can induce differentiation of PSCs into neural phenotypes including neurons. In this study, we encapsulated all-trans RA within poly (ɛ-caprolactone) (PCL) microspheres to generate controlled morphogen release over 28 days. RA/PCL microspheres less than ~10 μm in diameter were readily incorporated within the interstitial sites of human induced pluripotent stem cell (hiPSC) aggregates. After 5 days of culture, the microspheres did not induce cytotoxic effects and the hiPSC aggregates containing microspheres showed a decrease in the pluripotency marker SSEA-4. After 7 days of culture on laminin surfaces, aggregates expressed the neuronal marker TUJ1 and displayed extended neurite outgrowth. This approach provides consistent RA delivery throughout the aggregate and could be an effective strategy for differentiating cells in vivo. Overall, our results demonstrate that it is possible to combine hiPSC aggregates with RA/PCL microspheres for neural tissue engineering applications. en_US
dc.description.sponsorship The authors would like to thank funding from the University of Victoria, the Canada Research Chairs program, the Rick Hansen Foundation, and the Natural Science and Engineering Research Council for funding for this work. en_US
dc.language.iso en en_US
dc.publisher Springer en_US
dc.subject controlled release en_US
dc.subject drug delivery en_US
dc.subject neural tissue engineering en_US
dc.subject poly(ɛ-caprolactone) en_US
dc.subject embryoid body en_US
dc.title Incorporation of retinoic acid releasing microspheres into pluripotent stem cell aggregates for inducing neuronal differentiation en_US
dc.type Preprint en_US
dc.description.scholarlevel Faculty en_US
dc.description.reviewstatus Reviewed en_US

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