Clinical-grade extracellular vesicles derived from umbilical cord mesenchymal stromal cells: preclinical development and first-in-human intra-articular validation as therapeutics for knee osteoarthritis.

Osteoarthritis (OA) is a joint disease characterized by articular cartilage degradation. Persistent low-grade inflammation defines OA pathogenesis, with crucial involvement of pro-inflammatory M1-like macrophages. While mesenchymal stromal cells (MSC) and their small extracellular vesicles (sEV) hold promise for OA treatment, achieving consistent clinical-grade sEV products remains a significant challenge.

Safety and efficacy of mesenchymal stromal cells mitochondria transplantation as a cell-free therapy for osteoarthritis.

Objective: The inflammatory responses from synovial fibroblasts and macrophages and the mitochondrial dysfunction in chondrocytes lead to oxidative stress, disrupt extracellular matrix (ECM) homeostasis, and accelerate the deterioration process of articular cartilage in osteoarthritis (OA). In recent years, it has been proposed that mesenchymal stromal cells (MSC) transfer their functional mitochondria to damaged cells in response to cellular stress, becoming one of the mechanisms underpinning their therapeutic effects. Therefore, we hypothesize that a novel cell-free treatment for OA could involve direct mitochondria transplantation, restoring both cellular and mitochondrial homeostasis.

Mitochondrial transfer balances cell redox, energy and metabolic homeostasis in the osteoarthritic chondrocyte preserving cartilage integrity.

Osteoarthrosis (OA) is a leading cause of disability and early mortality, with no disease modifying treatment. Mitochondrial (MT) dysfunction and changes in energy metabolism, leading to oxidative stress and apoptosis, are main drivers of disease. In reaction to stress, mesenchymal stromal/stem cells (MSCs) donate their MT to damaged tissues.

A Phase I Dose-Escalation Clinical Trial to Assess the Safety and Efficacy of Umbilical Cord-Derived Mesenchymal Stromal Cells in Knee Osteoarthritis.

Osteoarthritis (OA) is the most common degenerative joint disease. Mesenchymal stromal cells (MSC) are promising cell-based therapy for OA. However, there is still a need for additional randomized, dose-dependent studies to determine the optimal dose and tissue source of MSC for improved clinical outcomes.