Sturm, Lisa; Schwemberger, Bettina; Menzel, Ursula; Häckel, Sonja; Albers, Christoph E.; Plank, Christian; Rip, Jaap; Alini, Mauro; Traweger, Andreas; Grad, Sibylle; Basoli, Valentina (2021). In Vitro Evaluation of a Nanoparticle-Based mRNA Delivery System for Cells in the Joint. Biomedicines, 9(7) MDPI 10.3390/biomedicines9070794
|
Text
biomedicines-09-00794-v2.pdf - Published Version Available under License Creative Commons: Attribution (CC-BY). Download (3MB) | Preview |
Biodegradable and bioresponsive polymer-based nanoparticles (NPs) can be used for oligonucleotide delivery, making them a promising candidate for mRNA-based therapeutics. In this study, we evaluated and optimized the efficiency of a cationic, hyperbranched poly(amidoamine)s-based nanoparticle system to deliver tdTomato mRNA to primary human bone marrow stromal cells (hBMSC), human synovial derived stem cells (hSDSC), bovine chondrocytes (bCH), and rat tendon derived stem/progenitor cells (rTDSPC). Transfection efficiencies varied among the cell types tested (bCH 28.4% ± 22.87, rTDSPC 18.13% ± 12.07, hBMSC 18.23% ± 14.80, hSDSC 26.63% ± 8.81) and while an increase of NPs with a constant amount of mRNA generally improved the transfection efficiency, an increase of the mRNA loading ratio (2:50, 4:50, or 6:50 w/w mRNA:NPs) had no impact. However, metabolic activity of bCHs and rTDSPCs was significantly reduced when using higher amounts of NPs, indicating a dose-dependent cytotoxic response. Finally, we demonstrate the feasibility of transfecting extracellular matrix-rich 3D cell culture constructs using the nanoparticle system, making it a promising transfection strategy for musculoskeletal tissues that exhibit a complex, dense extracellular matrix.
Item Type: |
Journal Article (Original Article) |
|---|---|
Division/Institute: |
04 Faculty of Medicine > Department of Orthopaedic, Plastic and Hand Surgery (DOPH) > Clinic of Orthopaedic Surgery |
UniBE Contributor: |
Häckel, Sonja, Albers, Christoph E. |
Subjects: |
600 Technology > 610 Medicine & health |
ISSN: |
2227-9059 |
Publisher: |
MDPI |
Language: |
English |
Submitter: |
Kathrin Aeschlimann |
Date Deposited: |
10 Nov 2021 16:12 |
Last Modified: |
05 Dec 2022 15:53 |
Publisher DOI: |
10.3390/biomedicines9070794 |
PubMed ID: |
34356857 |
Uncontrolled Keywords: |
biologicals bioresponsive polymer-based nanoparticles joint therapies therapeutic mRNA transfection |
BORIS DOI: |
10.48350/160112 |
URI: |
https://boris.unibe.ch/id/eprint/160112 |
Actions (login required)
 |
Edit item |