Artificial mitochondrial transplantation (AMT) reverses aging of mesenchymal stem cells and improves their immunomodulatory properties in LPS-induced synoviocytes inflammation.

This research investigates whether artificially transplanting mitochondria can rejuvenate Mesenchymal stem cells (MSCs), which have seen reduced therapeutic efficiency due to age, health condition, and growth rate decline. Studies using equine adipose-derived stromal cells (ASCs) revealed that ASCs receiving new mitochondria showed characteristics of decreased cell death and aging, improved insulin sensitivity, and better anti-inflammatory activity. The results suggest that artificial mitochondrial transplantation (AMT) may be a viable method for renewing the therapeutic viability of MSCs in patients.

Relevance of Mesenchymal Stem Cells (MSCs) to Regenerative Medicine

• Mesenchymal stem cells play a crucial role in regenerative medicine techniques, which aim to repair or restore injured or damaged tissues.
• However, issues relating to the patient’s age, health condition, and a decrease in MSC growth rates limit the effectiveness of autologous therapy, which uses the patients’ own cells for treatment.

Concept of Artificial Mitochondrial Transplantation (AMT)

• The research team sought to devise a strategy that would rejuvenate MSCs, thereby improving their therapeutic efficiency.
• In nature, mitochondrial transfer occurs between neighboring cells. The researchers attempted to mimic this process artificially in an approach they termed AMT.
• In the AMT experiment, mitochondria were isolated from healthy donor equine adipose-derived stromal cells (ASCs) and transferred to metabolically impaired recipient ASCs derived from horses affected by equine metabolic syndrome (EMS).

Results and Outcomes of AMT

• Following AMT, the recipient cells showed a decrease in apoptosis (cell death) and senescence (aging). They also exhibited lower endoplasmic reticulum stress and improved insulin sensitivity.
• Other results included an increase in mitochondrial fragmentation and associated PARKIN protein accumulation, indicating the elimination of dysfunctional organelles via the process of mitophagy – the selective degradation of mitochondria by autophagy.
• AMT also promoted physioxia, which refers to the physical state of having the optimal concentration of oxygen, and managed autophagy fluxes or the dynamics of autophagy activity.
• Importantly, the rejuvenated ASCs showed advances in their anti-inflammatory activity when introduced to LPS-stimulated synoviocytes, the cells that line the joints.

Significance of the Study

• These findings point to AMT as a potentially effective method for rejuvenating MSCs, this could drastically enhance the efficacy of autologous therapies.
• For patients whose MSCs have declined significantly due to their health condition, AMT could offer a significant improvement to their therapeutic prospects.