NDLI: Controlling mesenchymal stem cell gene expression using polymer-mediated delivery of siRNA

Content Provider	PubMed Central
Author	Benoit, Danielle S. W. Boutin, Molly E.
Abstract	siRNA treatment has great promise to specifically control gene expression and select cell behaviors but have delivery challenges limiting their use. Particularly for applications in regenerative medicine, uniform and consistent delivery of siRNA to control gene expression and subsequent stem cell functions, such as differentiation, is paramount. Therefore, a diblock copolymer was examined for its ability to effective delivery siRNA to mesenchymal stem cells (MSCs). The diblock copolymers, which are composed of cationic blocks for siRNA complexation, protection, and uptake and pH-responsive blocks for endosomal escape, were shown to facilitate nearly 100% MSC uptake of siRNA, which is vastly superior to a commercially-available control, DharmaFECT, which resulted in only ~60% siRNA positive MSCs. Moreover, the diblock copolymer, at conditions that result in excellent knockdown (down to ~10% of control gene expression), is cytocompatible, causing no negative effects on MSC survivability. In contrast, DharmaFECT:siRNA treatment results in only ~60% survivability of MSCs. Longitudinal knockdown after siRNA treatment was examined and protein knockdown persists for ~6 days regardless of delivery system (diblock copolymer or DharmaFECT). Finally, MSC phenotype and differentiation capacity was examined after treatment with control siRNA. There is no statistically significant differences on cell surface markers of diblock copolymer:siRNA or DharmaFECT:siRNA treated or cells measured 2 weeks after siRNA delivery compared to untreated cells. Upon differentiation with typical media/culture conditions to adipogenic, chondrogenic, and osteogenic lineages and examination of histological staining markers, there is no discernable differences between treated and untreated cells, regardless of delivery mechanism. Thus, diblock copolymers examined herein facilitate uniform siRNA treatment of MSCs, inducing siRNA-specific gene and protein knockdown without adversely affecting MSC survival or differentiation capacity and therefore show great promise for use within regenerative medicine applications.
Related Links	http://dx.doi.org/10.1021/bm301294n
Ending Page	3849
Page Count	9
Starting Page	3841
File Format	PDF
ISSN	15257797
e-ISSN	15264602
Journal	Biomacromolecules
Issue Number	11
Volume Number	13
Language	English
Publisher Date	2012-11-12
Access Restriction	Open
Subject Keyword	Materials Chemistry Bioengineering Polymers and Plastics Biomaterials Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Materials Chemistry Biomaterials Bioengineering Polymers and Plastics

Sl.	Authority	Responsibilities	Communication Details
1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
2	Indian Institute of Technology Kharagpur	Host Institute of the Project: The host institute of the project is responsible for providing infrastructure support and hosting the project	https://www.iitkgp.ac.in
3	National Digital Library of India Office, Indian Institute of Technology Kharagpur	The administrative and infrastructural headquarters of the project	Dr. B. Sutradhar bsutra@ndl.gov.in
4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
5	Website/Portal (Helpdesk)	Queries regarding NDLI and its services	support@ndl.gov.in
6	Contents and Copyright Issues	Queries related to content curation and copyright issues	content@ndl.gov.in
7	National Digital Library of India Club (NDLI Club)	Queries related to NDLI Club formation, support, user awareness program, seminar/symposium, collaboration, social media, promotion, and outreach	clubsupport@ndl.gov.in
8	Digital Preservation Centre (DPC)	Assistance with digitizing and archiving copyright-free printed books	dpc@ndl.gov.in
9	IDR Setup or Support	Queries related to establishment and support of Institutional Digital Repository (IDR) and IDR workshops	idr@ndl.gov.in

Engineering Surfaces for Substrate-Mediated Gene Delivery Using Recombinant Proteins

Pullulan Hydrogels Improve Mesenchymal Stem Cell Delivery into High-Oxidative-Stress Wounds

Synthesis of folate-functionalized RAFT polymers for targeted siRNA delivery

Cytosolic Delivery Mediated Via Electrostatic Surface Binding of Protein, Virus, or siRNA Cargos to pH-Responsive Core-Shell Gel Particles

Polymer-peptide delivery platforms: effect of oligopeptide orientation on polymer-based DNA delivery

Effects of Base Polymer Hydrophobicity and End Group Modification on Polymeric Gene Delivery

Efficient Intracellular siRNA Delivery by Ethyleneimine-Modified Amphiphilic Macromolecules

Facile Synthesis of Multivalent Folate-Block Copolymer Conjugates via Aqueous RAFT Polymerization: Targeted Delivery of siRNA and Subsequent Gene Suppression†

Characterization of Degradable Polyelectrolyte Multilayers Fabricated Using DNA βand a Fluorescently-Labeled Poly(β-amino ester): Shedding Light on the Role of the Cationic Polymer in Promoting Surface-Mediated Gene Delivery

Controlling mesenchymal stem cell gene expression using polymer-mediated delivery of siRNA

Similar Documents

Engineering Surfaces for Substrate-Mediated Gene Delivery Using Recombinant Proteins

Pullulan Hydrogels Improve Mesenchymal Stem Cell Delivery into High-Oxidative-Stress Wounds

Synthesis of folate-functionalized RAFT polymers for targeted siRNA delivery

Cytosolic Delivery Mediated Via Electrostatic Surface Binding of Protein, Virus, or siRNA Cargos to pH-Responsive Core-Shell Gel Particles

Polymer-peptide delivery platforms: effect of oligopeptide orientation on polymer-based DNA delivery

Effects of Base Polymer Hydrophobicity and End Group Modification on Polymeric Gene Delivery

Efficient Intracellular siRNA Delivery by Ethyleneimine-Modified Amphiphilic Macromolecules

Facile Synthesis of Multivalent Folate-Block Copolymer Conjugates via Aqueous RAFT Polymerization: Targeted Delivery of siRNA and Subsequent Gene Suppression†

Characterization of Degradable Polyelectrolyte Multilayers Fabricated Using DNA βand a Fluorescently-Labeled Poly(β-amino ester): Shedding Light on the Role of the Cationic Polymer in Promoting Surface-Mediated Gene Delivery

Controlling mesenchymal stem cell gene expression using polymer-mediated delivery of siRNA