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...
Saved in:
Main Authors: | , , , , |
---|---|
Other Authors: | |
Format: | Article |
Language: | English |
Published: |
2013
|
Online Access: | https://hdl.handle.net/10356/102226 http://hdl.handle.net/10220/10692 |
Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
Institution: | Nanyang Technological University |
Language: | English |
id |
sg-ntu-dr.10356-102226 |
---|---|
record_format |
dspace |
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 |
_version_ |
1681047396741545984 |