In Vitro Evaluation of a Nanoparticle-Based mRNA Delivery System for Cells in the Joint

Biomedicines, 2021 · DOI: 10.3390/biomedicines9070794 · Published: July 8, 2021

Pharmacology Biomedical Musculoskeletal Medicine

Simple Explanation

The study explores the use of nanoparticles (NPs) to deliver mRNA to cells in the joint. The goal is to develop a more effective treatment for musculoskeletal disorders. The NPs were tested on different cell types to see how well they could deliver mRNA and produce a desired protein (tdTomato). The researchers found that the effectiveness of mRNA delivery varied depending on the cell type. They also tested different amounts of NPs and mRNA to find the best combination for delivering mRNA without harming the cells. An optimal ratio of mRNA to NPs was determined. The study also showed that the NPs could deliver mRNA to cells in 3D cell cultures, which are more similar to tissues in the body. This suggests that the NPs could be a promising way to treat musculoskeletal disorders by delivering therapeutic mRNA to cells in the joint.

Study Duration

Not specified

Participants

Primary human bone marrow stromal cells (hBMSC), human synovial derived stem cells (hSDSC), bovine chondrocytes (bCH), and rat tendon derived stem/progenitor cells (rTDSPC)

Evidence Level

Not specified

Key Findings

1
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).
2
Increasing the amount of NPs generally improved transfection efficiency, but increasing the mRNA loading ratio had no impact.
3
Metabolic activity of bCHs and rTDSPCs was significantly reduced when using higher amounts of NPs, indicating a dose-dependent cytotoxic response.

Research Summary

This study evaluated 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, and while an increase of NPs with a constant amount of mRNA generally improved the transfection efficiency, an increase of the mRNA loading ratio had no impact. The study demonstrated 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.

Practical Implications

Therapeutic Potential

The NP-based delivery system has potential for mRNA-based treatment of musculoskeletal and joint-related pathologies.

Optimization Strategy

Optimization of mRNA:NP ratios can improve transfection efficiency while minimizing cytotoxicity.

3D Transfection

Feasibility of transfecting cells in 3D cultures suggests potential for in vivo applications.

Study Limitations

1
Further analysis is necessary to evaluate performance of the NP delivery system in a 3D environment.
2
Demonstration of the ability of the mRNA:NP complexes to penetrate the ECM and transfect cells embedded in their native matrices is necessary.
3
Further evaluation of the NPs in terms of biocompatibility and performance in vivo will be needed.

Your Feedback

Was this summary helpful?

Back to Pharmacology