FGF10 Rejuvenates Spinal Stem Cells to Reverse Disc Degeneration

Chronic low back pain is one of the most prevalent and disabling consequences of aging, and intervertebral disc degeneration (IVDD) is its single largest structural cause. Despite its enormous burden, no therapy currently reverses disc degeneration at the cellular level. This study, published in the Journal of Advanced Research, tackles that gap by asking what drives the loss of regenerative capacity in the disc and whether it can be reversed.

Using single-cell RNA sequencing (scRNA-seq) alongside bulk RNA sequencing of both clinical samples and animal models, the team identified a distinct stem cell subpopulation within the nucleus pulposus — the gel-like core of each disc — defined by surface expression of THY1 (CD90). This THY1-positive population retains significant stemness and regenerative potential, but it is markedly depleted as IVDD progresses, contributing directly to the disc's inability to self-repair.

RNA sequencing of senescent THY1+ nucleus pulposus stem cells (NPSCs) pointed to fibroblast growth factor 10 (FGF10) as the pivotal rejuvenation signal. In patient-derived IVDD tissue, FGF10 expression was diminished compared to healthy controls. Mechanistically, FGF10 binds FGFR1, which suppresses phosphorylation of the transcription factor CREB. Reduced CREB activity in turn downregulates ARG2, a regulator of mitochondrial fission mediated through DRP1. Restoring this pathway normalized mitochondrial dynamics and reversed cellular senescence in THY1+ NPSCs.

Transplantation of NPSCs engineered to overexpress FGF10 into animal IVDD models produced measurable disc regeneration, validating the therapeutic potential of the approach in vivo.

These findings position FGF10-FGFR1-CREB-ARG2-DRP1 as a tractable molecular axis for drug or cell-therapy development targeting disc aging. Limitations include reliance on the abstract alone, preclinical in vivo data, and the need for human clinical validation.