Direct reprogramming of mouse fibroblasts into neural cells via Porphyra yezoensis polysaccharide based high efficient gene co-delivery

Abstract Background The cell source for transplantation therapy is always a prerequisite question to be solved in clinical applications. Neural cells are considered non-regenerable, which highly restrict their application in the treatment for nerve injury. Therefore, neural trans-differentiation bas...

Full description

Bibliographic Details
Main Authors: Qingtong Yu, Jingjing Chen, Wenwen Deng, Xia Cao, Yan Wang, Jie Zhou, Wenqian Xu, Pan Du, Qiang Wang, Jiangnan Yu, Ximing Xu
Format: Article
Language:English
Published: BMC 2017-11-01
Series:Journal of Nanobiotechnology
Subjects:
Online Access:http://link.springer.com/article/10.1186/s12951-017-0317-y
_version_ 1798041234683461632
author Qingtong Yu
Jingjing Chen
Wenwen Deng
Xia Cao
Yan Wang
Jie Zhou
Wenqian Xu
Pan Du
Qiang Wang
Jiangnan Yu
Ximing Xu
author_facet Qingtong Yu
Jingjing Chen
Wenwen Deng
Xia Cao
Yan Wang
Jie Zhou
Wenqian Xu
Pan Du
Qiang Wang
Jiangnan Yu
Ximing Xu
author_sort Qingtong Yu
collection DOAJ
description Abstract Background The cell source for transplantation therapy is always a prerequisite question to be solved in clinical applications. Neural cells are considered non-regenerable, which highly restrict their application in the treatment for nerve injury. Therefore, neural trans-differentiation based on gene transfection provides a new solution to this issue. Compared to viral strategy, non-viral gene delivery systems are considered as a more promising way to achieve this aim. This study centers on a novel application of Porphyra yezoensis polysaccharide as a non-viral gene carrier for the neural trans-differentiation of mouse fibroblasts. Results Ethanediamine modified P. yezoensis polysaccharide (Ed-PYP) served as a gene carrier and a group of plasmids that encode Ascl1, Brn4, and Tcf3 (pABT) self-assembled into nanoparticles. Results demonstrated that Ed-PYP–pABT nanoparticles at Ed-PYP: pABT weight ratio of 40:1 was the optimal candidate for gene delivery. ELISA assay revealed the highest expression levels of NGF, BDNF and SHH at 14 days after last transfection. Immunofluorescence and western blot assays also showed robust expression of neural markers including Nestin, GFAP, β-3tubulin, NF200, GAP43 and MAP2, in induced 3T6 cells at this time point. Conclusion Overall, these findings indicated that the P. yezoensis polysaccharide-based non-viral gene co-delivery system is a promising strategy for the generation of neural cells, which might facilitate the developments in the recovery of neural injuries.
first_indexed 2024-04-11T22:18:38Z
format Article
id doaj.art-eb4b8aa78a3241cfa700724ebd266622
institution Directory Open Access Journal
issn 1477-3155
language English
last_indexed 2024-04-11T22:18:38Z
publishDate 2017-11-01
publisher BMC
record_format Article
series Journal of Nanobiotechnology
spelling doaj.art-eb4b8aa78a3241cfa700724ebd2666222022-12-22T04:00:17ZengBMCJournal of Nanobiotechnology1477-31552017-11-0115111510.1186/s12951-017-0317-yDirect reprogramming of mouse fibroblasts into neural cells via Porphyra yezoensis polysaccharide based high efficient gene co-deliveryQingtong Yu0Jingjing Chen1Wenwen Deng2Xia Cao3Yan Wang4Jie Zhou5Wenqian Xu6Pan Du7Qiang Wang8Jiangnan Yu9Ximing Xu10Department of Pharmaceutics, School of Pharmacy, and Center for Drug/Gene Delivery and Tissue Engineering, Jiangsu UniversityDepartment of Pharmaceutics, School of Pharmacy, and Center for Drug/Gene Delivery and Tissue Engineering, Jiangsu UniversityDepartment of Pharmaceutics, School of Pharmacy, and Center for Drug/Gene Delivery and Tissue Engineering, Jiangsu UniversityDepartment of Pharmaceutics, School of Pharmacy, and Center for Drug/Gene Delivery and Tissue Engineering, Jiangsu UniversityDepartment of Pharmaceutics, School of Pharmacy, and Center for Drug/Gene Delivery and Tissue Engineering, Jiangsu UniversityDepartment of Pharmaceutics, School of Pharmacy, and Center for Drug/Gene Delivery and Tissue Engineering, Jiangsu UniversityDepartment of Pharmaceutics, School of Pharmacy, and Center for Drug/Gene Delivery and Tissue Engineering, Jiangsu UniversityDepartment of Pharmaceutics, School of Pharmacy, and Center for Drug/Gene Delivery and Tissue Engineering, Jiangsu UniversityDepartment of Pharmaceutics, School of Pharmacy, and Center for Drug/Gene Delivery and Tissue Engineering, Jiangsu UniversityDepartment of Pharmaceutics, School of Pharmacy, and Center for Drug/Gene Delivery and Tissue Engineering, Jiangsu UniversityDepartment of Pharmaceutics, School of Pharmacy, and Center for Drug/Gene Delivery and Tissue Engineering, Jiangsu UniversityAbstract Background The cell source for transplantation therapy is always a prerequisite question to be solved in clinical applications. Neural cells are considered non-regenerable, which highly restrict their application in the treatment for nerve injury. Therefore, neural trans-differentiation based on gene transfection provides a new solution to this issue. Compared to viral strategy, non-viral gene delivery systems are considered as a more promising way to achieve this aim. This study centers on a novel application of Porphyra yezoensis polysaccharide as a non-viral gene carrier for the neural trans-differentiation of mouse fibroblasts. Results Ethanediamine modified P. yezoensis polysaccharide (Ed-PYP) served as a gene carrier and a group of plasmids that encode Ascl1, Brn4, and Tcf3 (pABT) self-assembled into nanoparticles. Results demonstrated that Ed-PYP–pABT nanoparticles at Ed-PYP: pABT weight ratio of 40:1 was the optimal candidate for gene delivery. ELISA assay revealed the highest expression levels of NGF, BDNF and SHH at 14 days after last transfection. Immunofluorescence and western blot assays also showed robust expression of neural markers including Nestin, GFAP, β-3tubulin, NF200, GAP43 and MAP2, in induced 3T6 cells at this time point. Conclusion Overall, these findings indicated that the P. yezoensis polysaccharide-based non-viral gene co-delivery system is a promising strategy for the generation of neural cells, which might facilitate the developments in the recovery of neural injuries.http://link.springer.com/article/10.1186/s12951-017-0317-yPorphyra yezoensisCationized polysaccharideGene co-delivery, nanoparticlesNanoparticlesNeural trans-differentiation
spellingShingle Qingtong Yu
Jingjing Chen
Wenwen Deng
Xia Cao
Yan Wang
Jie Zhou
Wenqian Xu
Pan Du
Qiang Wang
Jiangnan Yu
Ximing Xu
Direct reprogramming of mouse fibroblasts into neural cells via Porphyra yezoensis polysaccharide based high efficient gene co-delivery
Journal of Nanobiotechnology
Porphyra yezoensis
Cationized polysaccharide
Gene co-delivery, nanoparticles
Nanoparticles
Neural trans-differentiation
title Direct reprogramming of mouse fibroblasts into neural cells via Porphyra yezoensis polysaccharide based high efficient gene co-delivery
title_full Direct reprogramming of mouse fibroblasts into neural cells via Porphyra yezoensis polysaccharide based high efficient gene co-delivery
title_fullStr Direct reprogramming of mouse fibroblasts into neural cells via Porphyra yezoensis polysaccharide based high efficient gene co-delivery
title_full_unstemmed Direct reprogramming of mouse fibroblasts into neural cells via Porphyra yezoensis polysaccharide based high efficient gene co-delivery
title_short Direct reprogramming of mouse fibroblasts into neural cells via Porphyra yezoensis polysaccharide based high efficient gene co-delivery
title_sort direct reprogramming of mouse fibroblasts into neural cells via porphyra yezoensis polysaccharide based high efficient gene co delivery
topic Porphyra yezoensis
Cationized polysaccharide
Gene co-delivery, nanoparticles
Nanoparticles
Neural trans-differentiation
url http://link.springer.com/article/10.1186/s12951-017-0317-y
work_keys_str_mv AT qingtongyu directreprogrammingofmousefibroblastsintoneuralcellsviaporphyrayezoensispolysaccharidebasedhighefficientgenecodelivery
AT jingjingchen directreprogrammingofmousefibroblastsintoneuralcellsviaporphyrayezoensispolysaccharidebasedhighefficientgenecodelivery
AT wenwendeng directreprogrammingofmousefibroblastsintoneuralcellsviaporphyrayezoensispolysaccharidebasedhighefficientgenecodelivery
AT xiacao directreprogrammingofmousefibroblastsintoneuralcellsviaporphyrayezoensispolysaccharidebasedhighefficientgenecodelivery
AT yanwang directreprogrammingofmousefibroblastsintoneuralcellsviaporphyrayezoensispolysaccharidebasedhighefficientgenecodelivery
AT jiezhou directreprogrammingofmousefibroblastsintoneuralcellsviaporphyrayezoensispolysaccharidebasedhighefficientgenecodelivery
AT wenqianxu directreprogrammingofmousefibroblastsintoneuralcellsviaporphyrayezoensispolysaccharidebasedhighefficientgenecodelivery
AT pandu directreprogrammingofmousefibroblastsintoneuralcellsviaporphyrayezoensispolysaccharidebasedhighefficientgenecodelivery
AT qiangwang directreprogrammingofmousefibroblastsintoneuralcellsviaporphyrayezoensispolysaccharidebasedhighefficientgenecodelivery
AT jiangnanyu directreprogrammingofmousefibroblastsintoneuralcellsviaporphyrayezoensispolysaccharidebasedhighefficientgenecodelivery
AT ximingxu directreprogrammingofmousefibroblastsintoneuralcellsviaporphyrayezoensispolysaccharidebasedhighefficientgenecodelivery