Towards Partial Reprogramming to Treat Disc Degeneration

A great deal of attention is being given to partial reprogramming as a basis for regenerative therapies these days. It restores youthful gene expression in cells, and if the risk of cancer can be managed, then this may help a range of age-related degenerative conditions by improving tissue maintenance and function. Thus we should probably expect to see, in the years ahead, every narrowly focused research group produce and publish proof of concept studies that support the use of partial reprogramming for their area of interest. This happened for senolytic therapies to clear senescent cells, once that line of research was underway in earnest, and it will happen for partial reprogramming.

Rejuvenation of nucleus pulposus cells (NPCs) in degenerative discs can reverse intervertebral disc degeneration (IDD). Partial reprogramming is used to rejuvenate aging cells and ameliorate progression of aging tissue while avoiding formation of tumors resulting from classical reprogramming. Understanding the effects and potential mechanisms of partial reprogramming in degenerative discs provides insights for development of new therapies for IDD treatment.

The findings of the present study show that partial reprogramming through short-term cyclic expression of Oct-3/4, Sox2, Klf4, and c-Myc (OSKM) inhibits progression of IDD, and significantly reduces senescence related phenotypes in aging NPCs. Mechanistically, short-term induction of OSKM in aging NPCs activates energy metabolism as a "energy switch" by upregulating expression of Hexokinase 2 (HK2) ultimately promoting redistribution of cytoskeleton and restoring the aging state in aging NPCs. These findings indicate that partial reprogramming through short-term induction of OSKM has high therapeutic potential in the treatment of IDD.


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