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Incorporation of Retinoic Acid Releasing Microspheres into Pluripotent Stem Cell Aggregates for Inducing Neuronal Differentiation

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 reti... Full description

Journal Title: Cellular and Molecular Bioengineering 2015, Vol.8(3), pp.307-319
Main Author: Gomez, Jose
Other Authors: Edgar, John , Agbay, Andrew , Bibault, Emma , Montgomery, Amy , Mohtaram, Nima , Willerth, Stephanie
Format: Electronic Article Electronic Article
Language: English
Subjects:
ID: ISSN: 1865-5025 ; E-ISSN: 1865-5033 ; DOI: 10.1007/s12195-015-0401-z
Link: http://dx.doi.org/10.1007/s12195-015-0401-z
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recordid: springer_jour10.1007/s12195-015-0401-z
title: Incorporation of Retinoic Acid Releasing Microspheres into Pluripotent Stem Cell Aggregates for Inducing Neuronal Differentiation
format: Article
creator:
  • Gomez, Jose
  • Edgar, John
  • Agbay, Andrew
  • Bibault, Emma
  • Montgomery, Amy
  • Mohtaram, Nima
  • Willerth, Stephanie
subjects:
  • Controlled release
  • Drug delivery
  • Neural tissue engineering
  • Poly(ɛ-caprolactone)
  • Embryoid body
ispartof: Cellular and Molecular Bioengineering, 2015, Vol.8(3), pp.307-319
description: 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  µ m 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.
language: eng
source:
identifier: ISSN: 1865-5025 ; E-ISSN: 1865-5033 ; DOI: 10.1007/s12195-015-0401-z
fulltext: fulltext
issn:
  • 1865-5033
  • 18655033
  • 1865-5025
  • 18655025
url: Link


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titleIncorporation of Retinoic Acid Releasing Microspheres into Pluripotent Stem Cell Aggregates for Inducing Neuronal Differentiation
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descriptionPluripotent 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  µ m 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.
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abstractPluripotent 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  µ m 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.
copNew York
pubSpringer US
doi10.1007/s12195-015-0401-z
pages307-319
date2015-09