Advancements in extracellular vesicle targeted therapies for rheumatoid arthritis: insights into cellular origins, current perspectives, and emerging challenges.

Rheumatoid arthritis (RA) remains a challenging chronic autoimmune disorder characterized by persistent joint inflammation and damage. While modern regenerative strategies, encompassing cell/stem cell-based therapies, gene therapy, and tissue engineering, have advanced tissue repair efforts, a definitive cure for RA remains elusive. Consequently, there is growing interest in developing targeted therapies that directly address the underlying mechanisms driving RA pathogenesis, such as extracellular vesicles (EVs).

Cartilage tissue engineering using decellularized biomatrix hydrogel containing TGF-β-loaded alginate microspheres in mechanically loaded bioreactor.

Physiochemical tissue inducers and mechanical stimulation are both efficient variables in cartilage tissue fabrication and regeneration. In the presence of biomolecules, decellularized extracellular matrix (ECM) may trigger and enhance stem cell proliferation and differentiation. Here, we investigated the controlled release of transforming growth factor beta (TGF-β1) as an active mediator of mesenchymal stromal cells (MSCs) in a biocompatible scaffold and mechanical stimulation for cartilage tissue engineering.

Co-culture engineering: a promising strategy for production of engineered extracellular vesicle for osteoarthritis treatment.

The therapeutic effects of extracellular vesicles (EVs) have been identified as a significant factor in intercellular communication in different disease treatments, including osteoarthritis (OA). Compared to the conventional approaches in treating OA, EV therapy is a non-invasive and cell-free method. However, improving the yield of EVs and their therapeutic effects are the main challenges for clinical applications.

Higher ratios of chondrocyte to mesenchymal stem cells elevate the therapeutic effects of extracellular vesicles harvested from chondrocyte/mesenchymal stem cell co-culture on osteoarthritis in a rat model.

Extracellular vesicles (EVs) may have a key therapeutic role and offer an innovative treatment for osteoarthritis (OA). Studies have shown that ratio of MSC/chondrocyte could affect their therapeutic outcomes. Here, we investigate the chondrogenic potential and therapeutic effect of EVs derived from MSCs and chondrocytes in the naïve, chondrogenically primed, and co-culture states to treat OA.

A bioscaffold of decellularized whole osteochondral sheet improves proliferation and differentiation of loaded mesenchymal stem cells in a rabbit model.

As a Natural decellularized extracellular matrix, osteochondral tissue is the best scaffold for the restoration of osteoarthritis defects. Bioscaffolds have the most similarly innate properties like biomechanical properties and the preserved connection of the bone-to-cartilage border. Although, their compacity and low porosity particularly, are proven to be difficulties of decellularization and cell penetration.

Co-aggregation of MSC/chondrocyte in a dynamic 3D culture elevates the therapeutic effect of secreted extracellular vesicles on osteoarthritis in a rat model.

Extracellular vesicles (EVs) have therapeutic effects on osteoarthritis (OA). Some recent strategies could elevate EV's therapeutic properties including cell aggregation, co-culture, and 3D culture. It seems that a combination of these strategies could augment EV production and therapeutic potential.

Advanced Nanotechnology Approaches as Emerging Tools in Cellular-Based Technologies.

Stem cells are valuable tools in regenerative medicine because they can generate a wide variety of cell types and tissues that can be used to treat or replace damaged tissues and organs. However, challenges related to the application of stem cells in the scope of regenerative medicine have urged scientists to utilize nanomedicine as a prerequisite to circumvent some of these hurdles. Nanomedicine plays a crucial role in this process and manipulates surface biology, the fate of stem cells, and biomaterials.

Engineering strategies for customizing extracellular vesicle uptake in a therapeutic context.

Extracellular vesicles (EVs) are advanced therapeutic strategies that can be used to efficiently treat diseases. Promising features of EVs include their innate therapeutic properties and ability to be engineered as targeted drug delivery systems. However, regulation of EV uptake is one challenge of EV therapy that must be overcome to achieve an efficient therapeutic outcome.

Targeted mesenchymal stem cell therapy equipped with a cell-tissue nanomatchmaker attenuates osteoarthritis progression.

Mesenchymal stem cells (MSCs) are at the forefront of research for a wide range of diseases, including osteoarthritis (OA). Despite having attracted the attention of orthopedists, current MSC therapy techniques are limited by poor MSC implantation in tissue defects and lack of lateral tissue integration, which has restricted the efficacy of cell therapy to alleviate OA symptoms only. Here, we developed targeted MSC therapy for OA cartilage using a cell-tissue matchmaking nanoconstruct (C-TMN).

Mesenchymal Stem Cell Therapy for Osteoarthritis: Practice and Possible Promises.

Osteoarthritis (OA) is a common progressively degenerative joint disease that affects more than 300 million people worldwide. OA is manifested by articular cartilage degradation, chronic pain, deformity, functional disability, and decreased quality of life. A real challenge in OA management is the lack of an effective cure because exiting therapeutics often provide symptom control rather than disease modification; therefore, they fail to prevent disease progression.

Electrospun PCL scaffold modified with chitosan nanoparticles for enhanced bone regeneration.

The encapsulation of ascorbic acid within chitosan nanoparticles (CHNs), embedded in a fibrous structure of a dexamethasone (Dex)-loaded PCL scaffold, provides a new plan for osteogenic differentiation of mesenchymal stem cells. This electrospun PCL fibrous scaffold can release Dex, as bone differentiation initiator, and ascorbic acid, as bone differentiation enhancer, in an approximately sustained release pattern for about 2 weeks. Ascorbic acid-loaded CHNs were prepared by electrospraying a mixture of chitosan and ascorbic acid, and Dex-containing PCL fibers were prepared by electrospinning a mixture of PCL and Dex.

Cartilage Repair by Mesenchymal Stem Cell-Derived Exosomes: Preclinical and Clinical Trial Update and Perspectives.

Osteoarthritis (OA) and other degenerative joint diseases are characterized by articular cartilage destruction, synovial inflammation, sclerosis of subchondral bone, and loss of extracellular matrix (ECM). Worldwide, these diseases are major causes of disability. Cell therapies have been considered to be the best therapeutic strategies for long-term treatment of articular cartilage diseases.

Microarray analysis identification of key pathways and interaction network of differential gene expressions during osteogenic differentiation.

Background: Adult bone marrow-derived mesenchymal stem cells (BM-MSCs) are multipotent stem cells that can differentiate into three lineages. They are suitable sources for cell-based therapy and regenerative medicine applications. This study aims to evaluate the hub genes and key pathways of differentially expressed genes (DEGs) related to osteogenesis by bioinformatics analysis in three different days.

Epidrugs: novel epigenetic regulators that open a new window for targeting osteoblast differentiation.

Efficient osteogenic differentiation of mesenchymal stem cells (MSCs) is a critical step in the treatment of bone defects and skeletal disorders, which present challenges for cell-based therapy and regenerative medicine. Thus, it is necessary to understand the regulatory agents involved in osteogenesis. Epigenetic mechanisms are considered to be the primary mediators that regulate gene expression during MSC differentiation.

Inhibition of hypertrophy and improving chondrocyte differentiation by MMP-13 inhibitor small molecule encapsulated in alginate-chondroitin sulfate-platelet lysate hydrogel.

Background: Mesenchymal stem cells are a promising cell source for chondrogenic differentiation and have been widely used in several preclinical and clinical studies. However, they are prone to an unwanted differentiation process towards hypertrophy that limits their therapeutic efficacy. Matrix metallopeptidase 13 (MMP-13) is a well-known factor regulated during this undesirable event.

Dual functional construct containing kartogenin releasing microtissues and curcumin for cartilage regeneration.

Background: Regeneration of articular cartilage poses a tremendous challenge due to its limited self-repair capability and inflammation at the damaged site. To generate the desired structures that mimic the structure of native tissue, microtissues with repeated functional units such as cell aggregates have been developed. Multicellular aggregates of mesenchymal stem cells (MSCs) can be used as microscale building blocks of cartilage due to their potential for cell-cell contact, cell proliferation, and differentiation.

Engineered-extracellular vesicles as an optimistic tool for microRNA delivery for osteoarthritis treatment.

Worldwide, osteoarthritis (OA) is one of the most common chronic diseases. In OA, profiling gene expression changes occur and cartilage tissue homeostasis is lost. Suggestions for OA treatment include regulation of gene expressions via the use of microRNAs (miRNAs).

Smart Polymeric Systems: A Biomedical Viewpoint.

Stimuli-responsive polymers (SRPs) are a recent innovative approach that has numerous biomedical applications. These smart polymers can be used in various industrial and medical areas. Smart polymeric hydrogels are a new class of biomedical materials that have attracted much attention in recent years.

Decellularized Extracellular Matrix as a Potent Natural Biomaterial for Regenerative Medicine.

Decellularization technique is a favorable method used to fabricate natural and tissue-like scaffolds. This technique is important because of its remarkable ability to perfectly mimic the natural extracellular matrix (ECM). ECM-based scaffolds/hydrogels provide structural support for cell differentiation and maturation.

The Importance of Stem Cell Senescence in Regenerative Medicine.

Mesenchymal stem cells (MSCs) are an interesting tool in regenerative medicine and a unique cell-based therapy to treat aging-associated diseases. Successful MSC therapy needs a large-scale cell culture, and requires a prolonged in vitro cell culture that subsequently leads to cell senescence. Administration of senescent MSCs results in inefficient cell differentiation in the clinical setting.

3D-porous β-tricalcium phosphate-alginate-gelatin scaffold with DMOG delivery promotes angiogenesis and bone formation in rat calvarial defects.

Hypoxia-inducible factor-1α (HIF-1α), a well-studied angiogenesis pathway, plays an essential role in angiogenesis-osteogenesis coupling. Targeting the HIF-1a pathway frequently leads to successful reconstruction of large-sized bone defects through promotion of angiogenesis. Dimethyloxalylglycine (DMOG) small molecule regulates the stability of HIF-1α at normal oxygen tension by mimicking hypoxia, which subsequently accelerates angiogenesis.

Regenerative Medicine Applications of Mesenchymal Stem Cells.

A major research challenge is to develop therapeutics that assist with healing damaged tissues and organs because the human body has limited ability to restore the majority of these tissues and organs to their original state. Tissue engineering (TE) and regenerative medicine (RM) promises to offer efficient therapeutic biological strategies that use mesenchymal stem cells (MSCs). MSCs possess the capability for self-renewal, multilineage differentiation, and immunomodulatory properties that make them attractive for clinical applications.