Nail proximal fold stem cells participate in nail growth, orchestrating enhanced digit regeneration via bone...

Area of Science:

• Stem cell biology
• Regenerative medicine
• Developmental biology

Background:

• Rodent and primate digit tips regenerate via nail stem cells (NSCs) and Wnt signaling.
• Nail proximal fold stem cells (NPFSCs) are bi-functional, contributing to epidermis and nail plate (NP).

Purpose of the Study:

• To investigate the role of NPFSCs and BMP signaling in digit regeneration.
• To elucidate the regulatory mechanisms of NPFSC-driven regeneration and potential therapeutic applications.

Main Methods:

• Inhibition and activation of BMP signaling in vivo.
• Analysis of nail plate structure and regeneration after amputation.
• BMP gain-of-function (GoF) models.
• Isolation, culture, and transplantation of lineage-traced NPFSCs.

Main Results:

• BMP signaling is a key regulator of NPFSC activity in nail growth and digit regeneration.
• BMP inhibition led to epidermalization and impaired Wnt activation, limiting regeneration.
• BMP activation enhanced NPFSC involvement, accelerated nail and bone regrowth, and enabled regeneration after significant P3 amputation.
• Transplanted NPFSCs integrated and contributed to nail matrix regeneration in vivo, demonstrating therapeutic potential.

Conclusions:

• BMP signaling is pivotal in mediating NPFSC-driven digit regeneration.
• BMP-Wnt cross-talk is essential for nail matrix cell activation and successful regeneration.
• NPFSCs hold therapeutic potential for enhancing regenerative outcomes after traumatic amputation.