Restoring sweat gland function in mice using regenerative sweat gland cells derived from chemically reprogrammed human epidermal keratinocytes

The regeneration of sweat glands(SwGs)plays a pivotal role in the functional recovery of extensive skin wounds.Recent research has illuminated the possibility of reprogramming human epidermal ker-atinocytes(HEKs)into induced SwG cells through the ectopic expression of ectodysplasin A.However,the clinical application of this genetic manipulation approach is inherently limited.In this study,we pre-sent findings demonstrating that a combination of six compounds can effectively and speedily reprogram HEKs in culture into fully functional SwG cells.These chemically induced SwG-like cells(ciSGCs)closely resemble the morphology,phenotypes,and functional properties of human primary SwG ductal cells.Furthermore,ciSGCs can be stimulated to differentiate into mature SwG cell types in vitro.In a 3D culture system,they can also generate SwG organoids that exhibit structural and biological features akin to native SwGs.Upon transplantation into scalded mouse paw skin,ciSGCs significantly expedited cuta-neous wound healing and completely restored the structural and functional aspects of the SwGs.In con-clusion,the small molecule cocktail-directed SwG reprogramming offers a non-transgenic and controllable strategy for producing high-quality,clinical-grade SwG cells,showing immense potential for the treatment of burn patients.

α-Ionone protects against UVB-induced photoaging in epidermal keratinocytes

Objective: To evaluate whether α-ionone, an aromatic compound mainly found in raspberries, carrots,roasted almonds, fruits, and herbs, inhibits UVB-mediated photoaging and barrier dysfunction in a human epidermal keratinocyte cell line(HaCaT cells).Methods: The anti-photoaging effect of α-ionone was evaluated by detecting the expression of barrierrelated genes and matrix metalloproteinases(MMPs) in HaCaT cells. The levels of reactive oxygen species,oxidation product, antioxidant enzyme, and inflammatory factors were further analysed to underline the protective effect of α-ionone on epidermal photoaging.Results: It was found that α-ionone attenuated UVB-induced barrier dysfunction by reversing keratin 1and filaggrin in HaCaT cells. α-Ionone also reduced the protein amount of MMP-1 and mRNA expression of MMP-1 and MMP-3 in UVB-irradiated HaCaT cells, implying protective effects on extracellular matrix.Furthermore, HaCaT cells exposed to α-ionone showed significant decreases in interleukin(IL)-1β, IL-6,IL-8, and tumor necrosis factor-α as compared to UVB-irradiated HaCaT cells. α-Ionone treatment significantly inhibited the UVB-induced intracellular reactive oxygen species increase and malondialdehyde accumulation. Therefore, the beneficial effects of α-ionone on inhibiting MMPs secretion and barrier damage may be related to attenuated inflammation and oxidative stress.Conclusion: Our results highlight the protective effects of α-ionone on epidermal photoaging and promote its clinic application as a potential natural anti-photodamage agent in future.

Study on the effects of alternating capacitive electric fields with different frequencies on promoting wound healing

Some researches to facilitate wound healing by using electrical stimulation are based on electric current stimulation,which may cause secondary damage and the imbalance of the microenvironment in vivo.In this study,alternating capacitive electric field(ACEF)was applied via a self-designed system so as to avoid direct contact with cells and to maintain stable microenvironment for cell growth.The influences of 58 mV/mm ACEFs with various frequencies of 10,60 and 110 Hz on epidermal cells,fibroblasts and macrophages which involve in wound healing were comprehensively explored.The results suggested that ACEFs of 10,60 and 110 Hz all significantly promoted the proliferation of human dermal fibroblasts(HDFs)and human epidermal keratinocyte cell line(HaCaT)cells,and 60 Hz ACEF furtherly accelerated the migration of these two kinds of cells.Moreover,ACEFs of all different studied frequencies facilitated M2-type polarization of macrophages,and YAP/TAZ expression of macrophages were enhanced under the stimulations of 10 and 60 Hz ACEFs.The enhancements in cell activity,migration rate and M2-type polarizability indicated that 58 mV/mm ACEFs especially at 60 Hz possessing potentially affirmative applications for wound healing without the risks of secondary damage and microenvironment imbalance.