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Osteoarthritis (OA) is a degenerative joint disease with limited therapeutic options, where inflammation plays a critical role in disease progression. Extracellular vesicles (EV) derived from mesenchymal stromal cells (MSC) have shown potential as a therapeutic approach for OA by modulating inflammation and alleviating degenerative processes in the joint. This study evaluated the therapeutic effects for the treatment of OA of two types of EV-exosomes and matrix-bound nanovesicles (MBV)-both derived from the human umbilical cord MSC (UC-MSC) via differential ultracentrifugation. Different phenotypes of human monocyte-derived macrophages (MDM) were used to study the anti-inflammatory properties of EV in vitro, and the medial meniscectomy-induced rat model of knee osteoarthritis (MMx) was used in vivo. The study found that both EV reduced pro-inflammatory cytokines IL-6 and TNF-α in MDM. However, exosomes showed superior results, preserving the extracellular matrix (ECM) of hyaline cartilage, and reducing synovitis more effectively than MBVs. Additionally, exosomes downregulated inflammatory markers (TNF-α, iNOS) and increased Arg-1 expression in macrophages and synovial fibroblasts, indicating a stronger anti-inflammatory effect. These results suggest UC-MSC exosomes as a promising therapeutic option for OA, with the potential for modulating inflammation and promoting joint tissue regeneration.
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http://dx.doi.org/10.3390/ijms252111564 | DOI Listing |
Biomater Adv
October 2025
Department of Orthopedic Surgery, School of Medicine, Ajou University, Suwon, Republic of Korea; Cell Therapy Center, Ajou Medical Center, Suwon, Republic of Korea; Department of Molecular Science and Technology, Ajou University, Suwon, Republic of Korea. Electronic address:
Decellularized extracellular matrix (dECM) exhibits tissue-specific pro- or anti-angiogenic effects. Previous studies have demonstrated that matrix-bound nanovesicles (MBVs) act as key bioactive components of dECM, replicating various biological functions such as anti-inflammatory and immunomodulatory effects. Building on this evidence, this study hypothesized that MBVs derived from cartilage and small intestinal submucosa (SIS) modulate angiogenesis through the selective packaging of miRNAs.
View Article and Find Full Text PDFACS Appl Mater Interfaces
March 2025
Department of Chemical and Biomedical Engineering, FAMU-FSU College of Engineering, Florida State University, Tallahassee, Florida 32310, United States.
Extracellular vesicles (EVs) are membrane-bound nanovesicles that show significance in intercellular communications and high therapeutic potential. In this study, a novel type of EV subpopulation, matrix-bound nanovesicles (MBVs), was identified from a decellularized extracellular matrix of brain organoids that were derived from human pluripotent stem cells to compare with supernatant EVs (SuEVs) isolated from spent media. The organoids generated 10-fold more MBVs than did SuEVs.
View Article and Find Full Text PDFTissue Eng Part A
February 2025
McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
Bioscaffolds composed of extracellular matrix (ECM) have been shown to promote a profound transition in macrophages and T-cells from a proinflammatory to a prohealing phenotype with associated site-appropriate and constructive tissue remodeling rather than scar tissue formation. Matrix-bound nanovesicles (MBV) are a distinct class of extracellular vesicles that can be isolated from the ECM and can recapitulate these immunomodulatory effects on myeloid cells and , as shown in multiple preclinical models of inflammatory-driven diseases. However, the effect of this MBV-mediated immunomodulation upon the ability to mount an adaptive immune response following pathogenic challenge is unknown.
View Article and Find Full Text PDFInt J Cardiol
February 2025
Department of Surgery, Pittsburgh, PA 15213, USA; McGowan Institute for Regenerative Medicine, Pittsburgh, PA 15213, USA; Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA. Electronic address:
Aims: Remodeling of the extracellular matrix (ECM) is critical for effective wound healing and maintaining organ homeostasis. The ECM of soft tissues, including cardiac, contains embedded nanovesicles; or matrix-bound nanovesicles (MBV). The luminal cargo of MBV consists of lipids, microRNAs (miRNAs), and proteins that influence the function of immune and stromal cells.
View Article and Find Full Text PDFInt J Mol Sci
October 2024
Institute for Regenerative Medicine, I. M. Sechenov First Moscow State Medical University, 119991 Moscow, Russia.
Osteoarthritis (OA) is a degenerative joint disease with limited therapeutic options, where inflammation plays a critical role in disease progression. Extracellular vesicles (EV) derived from mesenchymal stromal cells (MSC) have shown potential as a therapeutic approach for OA by modulating inflammation and alleviating degenerative processes in the joint. This study evaluated the therapeutic effects for the treatment of OA of two types of EV-exosomes and matrix-bound nanovesicles (MBV)-both derived from the human umbilical cord MSC (UC-MSC) via differential ultracentrifugation.
View Article and Find Full Text PDF