Mitochondria transfer from mesenchymal stem cells into osteoarthritic chondrocytes ameliorate cellular functions and...

Osteoarthritis, a common age-related joint disease, causes cartilage degeneration, leading to pain and disability. While pain management exists, cartilage regeneration options are limited. Exogenous mitochondria transfer is a novel regenerative approach. This study aimed to investigate the effects of exogenous mitochondrial transfer on cellular function, oxidative stress, inflammation, and apoptosis in osteoarthritic chondrocytes.

Two inflammatory models using M1-macrophage conditioned medium or co-culture with synovial fluid mesenchymal stem cells (MSCs) were established. The study compared mitochondria from Wharton's jelly (WJ-) and bone marrow (BM-) MSCs by analyzing their transfer to these models. Transfer effects were evaluated by mitochondrial membrane potential, cell viability, apoptosis, gene expression, and oxidative state.

Mitochondria tracking showed high transfer efficiencies (99.62 % for WJ-MSCs, 91.34 % for BM-MSCs). Late apoptosis was significantly reduced after transfer of WJ-MSCs mitochondria from 5.58 % to 2.93 % in the model with M1-macrophage conditioned medium. Expression of TNF-α and IL-1β was reduced after mitochondrial delivery. The expression of Ki67 was induced in parallel with increased ATP production and reduced HMOX-1 expression levels after the transfer. A decrease of 2.5- and 5-fold in ATP levels in cells after the inflammatory models were recovered after WJ-MSCs mitochondria transfer by 3.1- and 100-fold depending on the inflammatory model used. Although ROS levels remained unchanged, MDA levels decreased, and collagen type-2 expression increased.

Mitochondria transfer improved key aspects of chondrocyte dysfunction in inflammatory osteoarthritis models. These findings support its therapeutic potential for treating or slowing osteoarthritis by directly improving damaged chondrocyte health and function.