Researchers have discovered a promising new method for potentially treating osteoarthritis (OA), a debilitating joint disease for which there are currently no effective therapies.

This innovative approach uses mitochondrial transfer from mesenchymal stromal cells (MSCs)  isolated from  donated newborn umbilical cords to restore metabolic health in damaged cartilage. Rather than treating symptoms, this technique targets the cellular dysfunction at the heart of OA, addressing an unmet medical need in patient care.

Osteoarthritis is a complex disease characterized by mitochondrial dysfunction and energy starvation, leading to cell death and joint degeneration. With more than 300 million people affected worldwide, the need for effective treatments has never been greater. Traditional OA therapies focus primarily on pain and inflammation control, but a shift toward disease-modifying treatments is essential.

Research suggests that many OA phenotypes result from an energetic failure of chondrocytes, the only cellular component of healthy cartilage. This failure leads to increased oxidative stress, apoptosis and decreased ATP production.

The study, published in Theranostics, highlights an important mechanism: MSCs can directly donate their healthy mitochondria to chondrocytes isolated from OA patients, reviving their energy production and increasing their resistance to oxidative stress. Instead of injecting whole cells, the authors propose a method of transferring healthy mitochondria isolated from MSCs - previously tested in OA clinical trials - to preserve joint integrity and slow disease progression.

Angela Court, first author of the study, explains: "By transferring mitochondria from healthy stem cells to osteoarthritic cartilage cells, we can restore energy balance and reduce harmful oxidative stress. This cell-free approach addresses the underlying causes of cartilage degradation in OA at the cellular level.”

Dr. Maroun Khoury, corresponding author of the paper and director of the IMPACT Center of Excellence at the Universidad de los Andes in Santiago, Chile, adds: "In osteoarthritis, the power plants in cartilage cells become dysfunctional. Our approach provides new, efficient power generators. By transplanting healthy mitochondria, we're 'rewiring' the energy grid of damaged cartilage and potentially rejuvenating the entire joint ecosystem, probably through an anti-inflammatory effect. This will need to be demonstrated in future studies examining the effect on joint resident immune c

Dr. Fernando Figueroa, a rheumatologist and senior author of the article, states, "We are cautiously optimistic that this approach could lead to therapies that not only alleviate symptoms, but also slow or potentially reverse joint damage. Our findings are particularly exciting because they offer a new direction for OA treatment that focuses on modifying the disease process rather than just managing patient’s symptoms."

Next steps for the research team include further preclinical studies to optimize the treatment protocol understand the  biodistribution of the intra-articual injection of mitochondria and explore its long-term effects, with the hope of moving toward human clinical trials in the coming years.

Additional key findings of the study include:

1. Successful transfer of mitochondria from stem cells to osteoarthritic cartilage cells.
2. Restoration of energy production and metabolic balance in damaged cells.
3. Increased resistance to oxidative stress and cell death.
4. Improved joint health in a mouse model of osteoarthritis after mitochondrial transfer.

Dr. Patricia Luz-Crawford, a lead investigator, emphasizes, "Our research reveals a dynamic interaction between Mitochondria and chondrocytes that challenges the traditional view of cell therapy.  Understanding the metabolic shift in osteoarthritis is crucial as restoring energy balance can open new pathways for therapeutic strategies”.

This innovative approach addresses an unmet medical need in the treatment of OA and offers hope to millions of people worldwide who suffer from this debilitating disease. By targeting the cellular dysfunction in OA, mitochondrial transfer therapy could represent a significant advance in regenerative medicine for joint disease.

Reference

Court, A.C., Vega-Letter, A.M., Parra-Crisóstomo, E., Velarde, F., García, C., Ortloff, A., Vernal, R., Pradenas, C., Luz-Crawford, P., Khoury, M., Figueroa, F.E. (2024). Mitochondrial transfer balances cell redox, energy and metabolic homeostasis in the osteoarthritic chondrocyte preserving cartilage integrity. Theranostics, 14(17), 6471-6486.

https://www.thno.org/v14p6471.htm