An article published in the journal Biomaterials shows that CuS@MnO2 nanoparticles (NPs) synthesized with a short bacteriophage-selected mesenchymal stem cell (MSC) targeting peptide allowed the MSCs to take up these NPs. NP-modified MSCs produced greatly improved therapy of Rheumatoid Arthritis (RA) using stem cells.
Study: Highly effective rheumatoid arthritis therapy by peptide-promoted nanomodification of mesenchymal stem cells. Image Credit: Emily frost/Shutterstock.com
Current Treatments of Rheumatoid Arthritis
RA, which is marked by progressive joint degeneration and synovial inflammation, is one of the primary widespread inflammatory arthritis that affects around 1 % of the global population, however, it currently lacks an effective treatment.
Glucocorticoids (GCs), disease-modifying anti-rheumatic drugs (DMARDs) and non-steroidal anti-inflammatory drugs (NSAIDs) are the three main types of medications currently used in clinical practice.
GCs and NSAIDs can help with joint pain and stiffness, but they may cause side effects such as heart problems, osteoporosis, infections and gastric ulcers.
Standard DMARDs, like methotrexate (MTX), can lessen swelling by inhibiting the synthesis of pro-inflammatory cytokines and have little effect on cartilage degeneration. MTX, on the other hand, has a short plasma half-life and a poor concentration of the drug in the inflammatory region of the body.
Other side effects may also include liver and kidney damage, bone marrow depletion, and gastrointestinal problems. Biological DMARDs have been rapidly developed in recent years, though their action slows the progression of structural damage by reducing inflammation and have issues including drug resistance and the potential to cause significant infections and malignant tumors.
Mesenchymal Stem Cells as a Potential Treatment
Multilineage differentiation, inflammatory site and immunomodulation homing are all features of MSCs. These distinctive characteristics allow MSCs to become a potential treatment for a variety of inflammatory and degenerative diseases, including the treatment of RA, through cell therapy. Unfortunately, over 50 % of patients do not react to MSC treatment, and the therapeutic benefit of MSCs is only temporary.
Firstly, MSCs are susceptible to the inflammatory milieu and so lose their functions of immune-regulation when disclosed in an inflamed joint. Reactive oxygen species (ROS) are thought to be engaged in the inflammation development of RA and hence damaging to MSCs, as seen by the gradual decline in the quantity of MSCs in RA patients' synovial fluid.
Secondly, while the direct impacts of MSCs on tissue regeneration in RA are unknown, an evident clinical experiment found that MSC injections increased hyaline cartilage regeneration in RA patients. Nevertheless, the unregulated distinction of MSCs can also result in the development of tumors and the inability of cartilage repair.
As a result, it is important for an optimal stem cell strategy to include MSCs that have the ability to preserve their bio functions and chondrogenically develop to regenerate cartilage under the oxidative stress caused by RA.
Peptide-Promoted Nanomodification of MSCs for Enhanced RA Therapy
According to this study, RA therapy could be enhanced by short targeting peptide-promoted nanomodification of MSCs. To begin with, CuS@Mn2 NPs were produced due to some of their elements' appealing features. Mn and Cu both are critical trace components in the human body, and they play a key role in the production of natural Mn superoxide dismutase (SOD) and Cu-Zn SOD, respectively.
Cu and Mn can also encourage stem cell chondrogenesis. The study further explains the modification of CuS@MnO2 NPs with MSC-targeting peptides to increase the passage of the nanoparticles into MSCs since transporting nanomaterials into modifications of MSCs is still a difficult task.
To make VQ-CuS@MnO2/MET NPs, VQ-CuS@MnO2 NPs were injected with metformin. Lastly, MSCs were allowed to take up these NPs and utilize them to effectively limit synovial inflammation and maintain cartilage structure, alleviating arthritic symptoms greatly.
Important Findings of the Study
This study demonstrates that VCMM-MCSs were created by engineering MSCs with catalase (CAT) and superoxide dismutase (SOD)- like activity using dynamically MSC-targeting VQ-CuS@MnO2/MET NPs.
The biological features of these cells required in stem cell treatment, such as chondrogenesis, anti-inflammation, cell migration, and increased survival under oxidative stress, were improved by VCMM-MCSs.
Consequently, the VCMM-MSCs injections reduced cartilage damage and synovial hyperplasia in adjuvant-induced arthritis (AIA) as well as collagen-induced arthritis (CIA) models, substantially reducing arthritic symptoms. Since oxidative stress is present in numerous degenerative and inflammatory disorders, this strategy of altering MSCs with NPs could be applied to treat a number of other disorders as well as to achieve faster tissue healing using stem cell therapy.
Lu, Y., Li, Z. et al. (2022). Highly effective rheumatoid arthritis therapy by peptide-promoted nanomodification of mesenchymal stem cells. Biomaterials. Available at: https://www.sciencedirect.com/science/article/pii/S0142961222001132?via%3Dihub