Scientists from the University of Warsaw have identified stem cells at the base of the nail as key drivers of fingertip regeneration and shown that activating a major cell-signalling pathway dramatically accelerates the regrowth of nails and bone after injury, according to a new study.
The findings, published in Nature Communications, show that boosting the BMP (Bone Morphogenetic Protein) signalling pathway not only speeds regeneration but also enables mice to recover from much larger fingertip injuries than previously thought possible.
Researchers at the Centre of New Technologies focused on stem cells in the proximal nail fold, the tissue at the base of the nail that protects the nail plate's growth site. They found that BMP signalling plays a central role in controlling regeneration by activating the WNT pathway, another key cell-signalling system involved in tissue growth and renewal.
"BMP signalling pathway has a crucial function already during embryonic development. Disruption of this pathway leads to serious developmental defects. To investigate its importance in adult tissue regeneration, we created a genetic mouse model that allowed us to precisely disable the response of selected cells to BMP signals," Anna Maria Puławska-Czub, PhD, from the Laboratory of Stem Cells, Tissue Development and Regeneration at the Centre of New Technologies, University of Warsaw, explained in an interview with PAP – Science in Poland.
When the researchers blocked BMP signalling, they observed severe defects in nail development. Instead of forming a hard nail plate, the tissue developed into a structure resembling soft epidermis. The nail bed became overgrown, the keratogenous zone disappeared and stem cells stopped dividing rapidly.
The team also found that inhibiting BMP prevented activation of the WNT signalling pathway, significantly impairing tissue regeneration.
"The results suggest that BMP acts as a regulator that determines the ability of stem cells to respond to WNT pathway signals. When this relationship was disrupted, the regeneration process was significantly impaired, and the amputated finger did not regain its normal structure or original size," the researcher said.
The contrast between mice with inactive and enhanced BMP signalling was striking. In animals where the pathway was disabled, the deformed nail had recovered only about 60% of its original length and surface area after nine weeks, while the damaged bone at the tip of the finger failed to regenerate.
By contrast, mice with overactivated BMP signalling achieved complete nail regeneration within three weeks of amputation, while the bone regained its original shape after about five weeks. On average, the regenerated nail plate was 25% longer than in untreated animals.
The researchers also found that enhanced BMP signalling extended the natural limits of regeneration. Mice were able to fully regenerate both nail and bone after losing around 60% of the fingertip, whereas spontaneous regeneration had previously been thought possible only after much smaller injuries.
"The most exciting moment of the entire project, however, was the observation of partial nail plate regrowth even after amputation of approximately 90% of the distal phalanx bone. This result suggests that appropriate modulation of molecular signals can partially restore the regenerative program even in situations previously considered completely irreversible," Puławska-Czub emphasised.
The study also marks the first successful isolation and laboratory cultivation of stem cells from the proximal nail fold.
"The greatest challenge was isolating specific cells from tissue measuring just a fraction of a millimetre. We used a special mouse model in which the cells were labelled with fluorescent proteins, allowing us to track them at every stage of isolation and culture," the researcher explained.
After transplantation, the cultured stem cells survived and actively contributed to tissue repair. Histological analyses showed they integrated into their natural stem cell niche, supplied the regenerating nail matrix and participated in forming a new nail plate, demonstrating that they retained their stem cell properties after culture and transplantation.
The researchers cautioned that the findings are based on a mouse model. However, they said a better understanding of the molecular mechanisms controlling nail and bone regeneration could eventually help develop new treatments for limb injuries and regenerative therapies in humans. (PAP)
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