Controlled release of dextrin-conjugated growth factors to support growth and differentiation of neural stem cells

An essential aspect of stem cell in vitro culture and in vivo therapy is achieving sustained levels of growth factors to support stem cell survival and expansion, while maintaining their multipotency and differentiation potential. This study investigated the ability of dextrin (~74,000 g/mol; 27.8 m...

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Main Authors: Elaine L. Ferguson, Sameza Naseer, Lydia C. Powell, Joseph Hardwicke, Fraser I. Young, Bangfu Zhu, Qian Liu, Bing Song, David W. Thomas
Format: Article
Language:English
Published: Elsevier 2018-12-01
Series:Stem Cell Research
Online Access:http://www.sciencedirect.com/science/article/pii/S1873506118302496
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author Elaine L. Ferguson
Sameza Naseer
Lydia C. Powell
Joseph Hardwicke
Fraser I. Young
Bangfu Zhu
Qian Liu
Bing Song
David W. Thomas
author_facet Elaine L. Ferguson
Sameza Naseer
Lydia C. Powell
Joseph Hardwicke
Fraser I. Young
Bangfu Zhu
Qian Liu
Bing Song
David W. Thomas
author_sort Elaine L. Ferguson
collection DOAJ
description An essential aspect of stem cell in vitro culture and in vivo therapy is achieving sustained levels of growth factors to support stem cell survival and expansion, while maintaining their multipotency and differentiation potential. This study investigated the ability of dextrin (~74,000 g/mol; 27.8 mol% succinoylation) conjugated to epidermal growth factor (EGF) and basic fibroblast growth factor (bFGF; or FGF-2) (3.9 and 6.7% w/w protein loading, respectively) to support the expansion and differentiation of stem cells in vitro via sustained, controllable growth factor release. Supplementation of mouse neural stem cells (mNSCs) with dextrin-growth factor conjugates led to greater and prolonged proliferation compared to unbound EGF/bFGF controls, with no detectable apoptosis after 7 days of treatment. Immunocytochemical detection of neural precursor (nestin) and differentiation (Olig2, MAP2, GFAP) markers verified that controlled release of dextrin-conjugated growth factors preserves stem cell properties of mNSCs for up to 7 days. These results show the potential of dextrin-growth factor conjugates for localized delivery of bioactive therapeutic agents to support stem cell expansion and differentiation, and as an adjunct to direct neuronal repair. Keywords: Polymer therapeutics, Biodegradable polymers, Growth factors, Neural stem cells, Controlled release
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spelling doaj.art-d0ba3d37481549e3969e6314d7acd88f2022-12-21T22:22:10ZengElsevierStem Cell Research1873-50612018-12-01336978Controlled release of dextrin-conjugated growth factors to support growth and differentiation of neural stem cellsElaine L. Ferguson0Sameza Naseer1Lydia C. Powell2Joseph Hardwicke3Fraser I. Young4Bangfu Zhu5Qian Liu6Bing Song7David W. Thomas8Oral and Biomedical Sciences, School of Dentistry, College of Biomedical and Life Sciences, Cardiff University, Heath Park, Cardiff CF14 4XY, UK; Cardiff Institute of Tissue Engineering and Repair, Cardiff University, 10 Museum Place, Cardiff, South Glamorgan, CF10 3BG, UK; Corresponding author at: Advanced Therapies Group, Oral and Biomedical Sciences, School of Dentistry, College of Biomedical and Life Sciences, Cardiff University, Heath Park, Cardiff CF14 4XY, UK.Oral and Biomedical Sciences, School of Dentistry, College of Biomedical and Life Sciences, Cardiff University, Heath Park, Cardiff CF14 4XY, UKOral and Biomedical Sciences, School of Dentistry, College of Biomedical and Life Sciences, Cardiff University, Heath Park, Cardiff CF14 4XY, UK; Cardiff Institute of Tissue Engineering and Repair, Cardiff University, 10 Museum Place, Cardiff, South Glamorgan, CF10 3BG, UKOral and Biomedical Sciences, School of Dentistry, College of Biomedical and Life Sciences, Cardiff University, Heath Park, Cardiff CF14 4XY, UK; Cardiff Institute of Tissue Engineering and Repair, Cardiff University, 10 Museum Place, Cardiff, South Glamorgan, CF10 3BG, UKOral and Biomedical Sciences, School of Dentistry, College of Biomedical and Life Sciences, Cardiff University, Heath Park, Cardiff CF14 4XY, UK; Cardiff Institute of Tissue Engineering and Repair, Cardiff University, 10 Museum Place, Cardiff, South Glamorgan, CF10 3BG, UKOral and Biomedical Sciences, School of Dentistry, College of Biomedical and Life Sciences, Cardiff University, Heath Park, Cardiff CF14 4XY, UKOral and Biomedical Sciences, School of Dentistry, College of Biomedical and Life Sciences, Cardiff University, Heath Park, Cardiff CF14 4XY, UKOral and Biomedical Sciences, School of Dentistry, College of Biomedical and Life Sciences, Cardiff University, Heath Park, Cardiff CF14 4XY, UK; Cardiff Institute of Tissue Engineering and Repair, Cardiff University, 10 Museum Place, Cardiff, South Glamorgan, CF10 3BG, UKOral and Biomedical Sciences, School of Dentistry, College of Biomedical and Life Sciences, Cardiff University, Heath Park, Cardiff CF14 4XY, UK; Cardiff Institute of Tissue Engineering and Repair, Cardiff University, 10 Museum Place, Cardiff, South Glamorgan, CF10 3BG, UKAn essential aspect of stem cell in vitro culture and in vivo therapy is achieving sustained levels of growth factors to support stem cell survival and expansion, while maintaining their multipotency and differentiation potential. This study investigated the ability of dextrin (~74,000 g/mol; 27.8 mol% succinoylation) conjugated to epidermal growth factor (EGF) and basic fibroblast growth factor (bFGF; or FGF-2) (3.9 and 6.7% w/w protein loading, respectively) to support the expansion and differentiation of stem cells in vitro via sustained, controllable growth factor release. Supplementation of mouse neural stem cells (mNSCs) with dextrin-growth factor conjugates led to greater and prolonged proliferation compared to unbound EGF/bFGF controls, with no detectable apoptosis after 7 days of treatment. Immunocytochemical detection of neural precursor (nestin) and differentiation (Olig2, MAP2, GFAP) markers verified that controlled release of dextrin-conjugated growth factors preserves stem cell properties of mNSCs for up to 7 days. These results show the potential of dextrin-growth factor conjugates for localized delivery of bioactive therapeutic agents to support stem cell expansion and differentiation, and as an adjunct to direct neuronal repair. Keywords: Polymer therapeutics, Biodegradable polymers, Growth factors, Neural stem cells, Controlled releasehttp://www.sciencedirect.com/science/article/pii/S1873506118302496
spellingShingle Elaine L. Ferguson
Sameza Naseer
Lydia C. Powell
Joseph Hardwicke
Fraser I. Young
Bangfu Zhu
Qian Liu
Bing Song
David W. Thomas
Controlled release of dextrin-conjugated growth factors to support growth and differentiation of neural stem cells
Stem Cell Research
title Controlled release of dextrin-conjugated growth factors to support growth and differentiation of neural stem cells
title_full Controlled release of dextrin-conjugated growth factors to support growth and differentiation of neural stem cells
title_fullStr Controlled release of dextrin-conjugated growth factors to support growth and differentiation of neural stem cells
title_full_unstemmed Controlled release of dextrin-conjugated growth factors to support growth and differentiation of neural stem cells
title_short Controlled release of dextrin-conjugated growth factors to support growth and differentiation of neural stem cells
title_sort controlled release of dextrin conjugated growth factors to support growth and differentiation of neural stem cells
url http://www.sciencedirect.com/science/article/pii/S1873506118302496
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