Targeted mesenchymal stem cell therapy equipped with a cell-tissue nanomatchmaker attenuates osteoarthritis progression
Osteoarthritis (OA) is a rapidly growing health problem that affects up to 240 million middle-aged and older people worldwide. OA compensation of profound chondrocyte loss and hypocellularity in cartilage texture followed by OA progression has not occurred through conventional therapeutic options, including pain medications and surgery. This is mainly due to the inadequate delivery of therapeutic cells to the injured articular cartilage. Researchers at Royan Institute have used a nanobiotechnology approach for targeted cell delivery into osteoarthritic articular cartilage by incorporating iron nanoparticles (NPs) equipped with antibodies. NPs exhibit unique flexibility for comprehensive surface modifications used in various applications. They can be attached to specific ligands and make the appropriate ligand-receptor binding at the target site. NP-mediated cell-tissue attachment can create a 3D microenvironment around the trapped cell enabling efficient interaction with growth factors and other factors involved in tissue integration and cell differentiation. Custom-built C-TMN was characterized, and its physicochemical properties were confirmed in vitro. The immunofluorescence assay and Prussian blue iron staining showed that C- TMN could more efficiently bind to MSCs than UIN (unconjugated iron oxide NPs).
They induced a rat OA model using intra-articular injections of monosodium iodoacetate to cause a partial cartilage defect. The cell-tissue matchmaking nanoconstruct (C-TMN) was efficiently linked to both healthy and osteoarthritic cartilage since both tissues contained collagen type II. It is possible to treat OA in a less invasive manner through a one-step approach without MSC injection. C-TMN may create a unique region around the trapped MSCs that can subsequently be part of the pericellular matrix (PCM) with a thickness of 2–4 µm. The PCM is rich in proteoglycans, collagen (types II, IV, and XI), and fibronectin and modulates AC (articular cartilage) homeostasis by impacting signal transduction into chondrocytes and maintaining chondrogenic differentiation. Evidence supports the hypothesis that PCM (the pericellular matrix) can be a primary factor in OA development and inhibition. The attachment of C-TMN to the surface of osteoarthritic cartilage tissue may also be a substrate for trapping endogenous progenitor cells in addition to exogenous MSCs. Their hypothesis was further supported by the fact that treated animals had slightly increased concentration of TNF-α, which is one of the critical mediators of inflammatory response.
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