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Skin grafts: KLF4, a new target for activating skin stem cells

In a study published in Nature Biomedical Engineering, a team from the Genomics and Radiobiology of Keratinopoiesis laboratory (LGRK/ IRCM) has shown that a transcription factor, KLF4, plays a key role in the proliferation of the stem cells in the epidermis. The discovery brings new therapeutic perspectives to regenerative medicine.

Published on 22 October 2019

The human epidermis renews itself entirely every month thanks to the stem cells located in its deepest, "basal" layer, but the genes and mechanisms involved in that process remain largely unknown. However, researchers from LGRK (IRCM/François Jacob Institute of Biology), in partnership with AFM-Téléthon and the University of Évry, have shed light on the role a transcription factor, KLF4, plays in the control of skin stem cells.

Their results hold promise in the setting of cutaneous regenerative medicine, particularly for the bioengineering of skin grafts for tissue reconstruction. Clinically, the discovery may bring new procedures for severe burns, chronic ulcers or breast reconstructions, for example.

The massive culturing of patient-derived epidermal cells (keratinocytes) is mandatory for the production of skin grafts, but the procedure may result in a loss of stem cell function and resultantly a loss of regenerative capacity. The LGRK team showed that downregulating the gene responsible for KLF4 favored the rapid expansion of functional skin stem cells without altering their genetic stability. The keratinocytes expanded in this manner showed greater regenerative capacity in in vitro skin reconstruction models and in in vivo grafts. KLF4 thus appears to be a new molecular target able to bring improvements to skin graft bioengineering.

These results have been shared through a press release.

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