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Groundbreaking discovery by University of Warsaw researchers: new stem cells control finger regeneration

Category: Main page, Research highlights

A team from the Laboratory of Stem Cells, Tissue Development and Regeneration at the Center for New Technologies (CeNT) of the University of Warsaw, led by Professor Krzysztof Kobielak, has published its research findings in the prestigious scientific journal *Stem Cells* (Oxford University Press), in an article titled “Nail Proximal Fold Stem Cells (NPFSCs) Participate In Nail Growth, Orchestrating Enhanced Digit Regeneration via BMP Signaling Activation” (https://doi.org/10.1093/stmcls/sxag028). The research presents new mechanisms responsible for limb regeneration. It reveals that the stem cells previously discovered by Professor Kobielak’s team are multifunctional and not only participate in nail growth and contribute to the formation of the periungual epidermis, but, crucially, play a key role in the regeneration of fingertips following amputation,” says Dr. Anna Puławska-Czub, the first author of the study.

The team demonstrated that activation of the BMP (Bone Morphogenetic Protein) signaling pathway is crucial and significantly enhances the regenerative capacity of the distal digits, whereas inhibition of BMP signaling leads to impaired regeneration and blocks activation of the WNT pathway. The interaction between the BMP–WNT pathways proved to be crucial for proper regeneration of the distal part of the fingers.

One of the most important findings is that increased BMP activity in nail proximal fold stem cells ( NPFSCs) accelerates nail and bone regrowth, extending the regeneration boundary proximally following finger amputation, which enables full finger regeneration even after removal of up to ~60% of their distal portion.

To investigate this, the team generated three independent lines of genetically modified mice in which the BMP signaling pathway was either completely inactivated or constantly activated in the proximal nail fold stem cells. This unique model of genetically modified animals allowed for precise manipulation of the BMP signaling pathway and for the labeling of nail stem cells, enabling their precise tracking during finger regeneration.

This confirmed the active role of proximal nail fold stem cells in finger regeneration following amputation and demonstrated that their proper function depends on and requires active BMP signaling in the proximal nail fold and nail epithelium, without which this regeneration is impaired,” notes Prof. Kobielak.

In our study, we were able to isolate and culture nail proximal fold stem cells (NPFSCs) for the first time. Interestingly, this allowed us to transplant the cultured stem cells under laboratory conditions into the distal portions of amputated fingers. “These cells were able to reintegrate into the proximal nail fold tissue after transplantation and retained their regenerative properties, actively participating in the regeneration of fingers following amputation,” says Dr. Anna Puławska-Czub.

Understanding the molecular mechanisms underlying finger regeneration may enable the development of therapeutic strategies aimed at regenerating fingers lost as a result of amputation in humans. “The results of this research represent an important step toward actively controlling the regeneration of tissues previously considered incapable of regeneration, with the potential to develop cell therapies using the newly discovered stem cells from the proximal nail fold,” emphasizes Prof. Krzysztof Kobielak.

Anna Pulawska-Czub, Alicja Olczak-Cossu, Tomasz D Pieczonka, Krzysztof Kobielak, “Nail Proximal Fold Stem Cells (NPFSCs) Participate In Nail Growth, Orchestrating Enhanced Digit Regeneration via BMP Signaling Activation”, Stem Cells, doi: 10.1093/stmcls/sxag028