The researchers employed epigenetic reprogramming using OSK factors—Oct4, Sox2, and Klf4—while deliberately excluding c-Myc due to its association with cancer.

Initial experiments demonstrated that an OSK plasmid significantly reduced markers of senescence and DNA damage in these nucleus pulposus cells, restoring their fundamental functions.

A recent study published in Nature Bone Research highlights a novel approach to combat aging-related back pain by reprogramming the epigenetics of spinal disc cells in a rat model.

Nucleus pulposus cells, which are crucial for maintaining spinal discs, undergo degeneration with age, impairing their ability to renew and sustain the extracellular matrix, ultimately leading to back issues.

To enhance cellular uptake of the OSK plasmid, the researchers engineered exosomes modified with Cavin2, which were filled with the plasmid to rejuvenate aging spinal cells.

These modified exosomes proved to be more effective in delivering the necessary factors to older cells compared to their unmodified counterparts.

In the rat model of intervertebral disc degeneration, those treated with Cavin2-modified, OSK-containing exosomes showed near-complete restoration of disc health just four weeks after treatment.

RNA sequencing results indicated an anti-aging effect, revealing reduced expression of genes linked to cellular senescence in the treated rats compared to controls.

While these results are promising, further research is essential to evaluate the potential of this approach for human treatments, as the study utilized a rat model that may not fully represent natural aging.

The challenge of delivering the necessary factors to nucleus pulposus cells led researchers to choose modified exosomes derived from youthful bone marrow stem cells.