Nanofiber-mediated release of retinoic acid and brain-derived neurotrophic factor for enhanced neuronal differentiation of neural progenitor cells

The treatment of an injured central nervous system using stem-cell-based regenerative medicine still faces considerable hurdles that need to be overcome. Chief among which is the lack of efficient strategies to generate functional neurons from stem cells. The sustained delivery of biochemical cues a...

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Main Authors: Low, Wei Ching, Rujitanaroj, Pim-On, Wang, Feng, Wang, Jun, Chew, Sing Yian
Other Authors: School of Chemical and Biomedical Engineering
Format: Article
Language:English
Published: 2013
Online Access:https://hdl.handle.net/10356/102226
http://hdl.handle.net/10220/10692
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Institution: Nanyang Technological University
Language: English
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spelling sg-ntu-dr.10356-1022262020-03-07T11:35:33Z Nanofiber-mediated release of retinoic acid and brain-derived neurotrophic factor for enhanced neuronal differentiation of neural progenitor cells Low, Wei Ching Rujitanaroj, Pim-On Wang, Feng Wang, Jun Chew, Sing Yian School of Chemical and Biomedical Engineering The treatment of an injured central nervous system using stem-cell-based regenerative medicine still faces considerable hurdles that need to be overcome. Chief among which is the lack of efficient strategies to generate functional neurons from stem cells. The sustained delivery of biochemical cues and synergistic topographical signaling from electrospun nanofibrous scaffolds may be a potential strategy to enhance neuronal differentiation of stem cells for therapeutic purposes. In this study, retinoic acid (RA) and brain-derived neurotrophic factor (BDNF) were encapsulated into a copolymer of ε-caprolactone and ethyl ethylene phosphate to form a multifunctional, electrospun nanofibrous scaffold. Sustained release of RA and BDNF was achieved for at least 7 and 14 days, respectively. Despite lower cumulative release of drugs as compared to bolus delivery to plain nanofibers (at least 2× and 50× lower for RA and BDNF, respectively), nanofiber-mediated delivery of RA and/or BDNF resulted in similar capacity for neuronal differentiation of mouse neural progenitor cells (NPCs). In addition, nanofiber topography significantly increased neuronal differentiation (with BDNF, 47.4 % Map2+ cells on 2D vs. 53.4 to 56.5 % on nanofibers, p < 0.05) and reduced glial cell differentiation. BDNF was a more potent inducer of neuronal differentiation than RA. RA supplementation alone resulted in minimal effect on NPC differentiation, and dual supplementation of RA and BDNF did not further enhance the neuronal differentiation of NPCs. Collectively, the results suggest that synergistic effects of nanofiber topography and sustained delivery of RA and/or BDNF may contribute towards the design of a multifunctional artificial stem cell niche for NPC neuronal differentiation. NMRC (Natl Medical Research Council, S’pore) 2013-06-26T03:17:52Z 2019-12-06T20:51:55Z 2013-06-26T03:17:52Z 2019-12-06T20:51:55Z 2013 2013 Journal Article Low, W. C., Rujitanaroj, P. O., Wang, F., Wang, J., & Chew, S. Y. (2013). Nanofiber-mediated release of retinoic acid and brain-derived neurotrophic factor for enhanced neuronal differentiation of neural progenitor cells. Drug Delivery and Translational Research. 2190-393X https://hdl.handle.net/10356/102226 http://hdl.handle.net/10220/10692 10.1007/s13346-013-0131-5 en Drug delivery and translational research © 2013 Controlled Release Society.
institution Nanyang Technological University
building NTU Library
country Singapore
collection DR-NTU
language English
description The treatment of an injured central nervous system using stem-cell-based regenerative medicine still faces considerable hurdles that need to be overcome. Chief among which is the lack of efficient strategies to generate functional neurons from stem cells. The sustained delivery of biochemical cues and synergistic topographical signaling from electrospun nanofibrous scaffolds may be a potential strategy to enhance neuronal differentiation of stem cells for therapeutic purposes. In this study, retinoic acid (RA) and brain-derived neurotrophic factor (BDNF) were encapsulated into a copolymer of ε-caprolactone and ethyl ethylene phosphate to form a multifunctional, electrospun nanofibrous scaffold. Sustained release of RA and BDNF was achieved for at least 7 and 14 days, respectively. Despite lower cumulative release of drugs as compared to bolus delivery to plain nanofibers (at least 2× and 50× lower for RA and BDNF, respectively), nanofiber-mediated delivery of RA and/or BDNF resulted in similar capacity for neuronal differentiation of mouse neural progenitor cells (NPCs). In addition, nanofiber topography significantly increased neuronal differentiation (with BDNF, 47.4 % Map2+ cells on 2D vs. 53.4 to 56.5 % on nanofibers, p < 0.05) and reduced glial cell differentiation. BDNF was a more potent inducer of neuronal differentiation than RA. RA supplementation alone resulted in minimal effect on NPC differentiation, and dual supplementation of RA and BDNF did not further enhance the neuronal differentiation of NPCs. Collectively, the results suggest that synergistic effects of nanofiber topography and sustained delivery of RA and/or BDNF may contribute towards the design of a multifunctional artificial stem cell niche for NPC neuronal differentiation.
author2 School of Chemical and Biomedical Engineering
author_facet School of Chemical and Biomedical Engineering
Low, Wei Ching
Rujitanaroj, Pim-On
Wang, Feng
Wang, Jun
Chew, Sing Yian
format Article
author Low, Wei Ching
Rujitanaroj, Pim-On
Wang, Feng
Wang, Jun
Chew, Sing Yian
spellingShingle Low, Wei Ching
Rujitanaroj, Pim-On
Wang, Feng
Wang, Jun
Chew, Sing Yian
Nanofiber-mediated release of retinoic acid and brain-derived neurotrophic factor for enhanced neuronal differentiation of neural progenitor cells
author_sort Low, Wei Ching
title Nanofiber-mediated release of retinoic acid and brain-derived neurotrophic factor for enhanced neuronal differentiation of neural progenitor cells
title_short Nanofiber-mediated release of retinoic acid and brain-derived neurotrophic factor for enhanced neuronal differentiation of neural progenitor cells
title_full Nanofiber-mediated release of retinoic acid and brain-derived neurotrophic factor for enhanced neuronal differentiation of neural progenitor cells
title_fullStr Nanofiber-mediated release of retinoic acid and brain-derived neurotrophic factor for enhanced neuronal differentiation of neural progenitor cells
title_full_unstemmed Nanofiber-mediated release of retinoic acid and brain-derived neurotrophic factor for enhanced neuronal differentiation of neural progenitor cells
title_sort nanofiber-mediated release of retinoic acid and brain-derived neurotrophic factor for enhanced neuronal differentiation of neural progenitor cells
publishDate 2013
url https://hdl.handle.net/10356/102226
http://hdl.handle.net/10220/10692
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