[40] found that EpiSCs transform into TDCs and express CK10 under physiological and pathological conditions. Get the latest public health information from CDC: https://www.coronavirus.gov, Get the latest research information from NIH: https://www.nih.gov/coronavirus, Find NCBI SARS-CoV-2 literature, sequence, and clinical content: https://www.ncbi.nlm.nih.gov/sars-cov-2/. In the therapy of chronic wounds, they can be administrated either topically or using different matrix like hydrogels, scaffolds, dermal substitutes and extracellular matrix (ECM) derivatives. In this review, we will dissect the biological process of adult skin wound healing and emphasize the importance of epidermal stem cells during the wound healing. Moreover, we discovered that p73 isoforms expressed in the skin (ΔNp73) enhance p63-mediated expression of keratinocyte genes during cellular reprogramming from a mesenchymal to basal keratinocyte-like cell. Keratin is an important structural protein of epidermal cells. In this paper, we review the characteristics of EPSCs and the mechanisms underlying their functions during wound healing. 4,6-diamidino-2-phenylindoleindole (DAPT), as a blocker of the Notch signaling pathway, can specifically block the action of γ-secretase, thereby preventing the activation of Notch [73]. Thus, hair follicle and its connective tissue sheath are attractive targets for the development of regenerative therapies due to its accessibility and richness of stem cells. The division mode of EpiSC is mainly asymmetric. As the contributions of EPSCs in wound healing and tissue regeneration have been increasingly attracting the attention of researchers, a rising number of therapies based on EPSCs are currently under development. among numerous stem cells, epidermal stem cells (eScs) are the preferred choice for therapeutic approaches in terms of burn wounds due to their high availability and lack of ethical concerns, such as those for embryonic stem cells. Among other Regenerative Medicine basics, she discusses properties of epidermal stem cells, the physiology of wounds and the role of epidermal stem cells in wound healing. Epidermal Stem Cells in Wound Healing and Regeneration, Department of Burn Surgery, The First People’s Hospital of Foshan, Foshan 528000, China, Department of Medical Cosmetology, Jiangxi Maternal and Child Health Hospital, Nanchang 330006, China, Department of Burn Surgery, First Affiliated Hospital of Sun Yat-Sen University, Guangzhou 512100, China, S. Ghazizadeh and L. B. Taichman, “Multiple classes of stem cells in cutaneous epithelium: a lineage analysis of adult mouse skin,”, T. Tumbar, G. Guasch, V. Greco et al., “Defining the epithelial stem cell niche in skin,”, M. Korbling and Z. Estrov, “Adult stem cells for tissue repair — a new therapeutic concept?”, J. L. Xie, T. Z. Li, S. H. Qi et al., “A preliminary study on the identification and distribution of epidermal stem cells in different degrees of burn wounds in scalded rats,”, S. H. Qi, P. Liu, J. L. Xie et al., “Experimental study on repairing of nude mice skin defects with composite skin consisting of xenogeneic dermis and epidermal stem cells and hair follicle dermal papilla cells,”, M. Isakson, C. de Blacam, D. Whelan, A. McArdle, and A. J. P. Clover, “Mesenchymal stem cells and cutaneous wound healing: current evidence and future potential,”, A. Nuschke, “Activity of mesenchymal stem cells in therapies for chronic skin wound healing,”, M. S. Choudhery, M. Khan, R. Mahmood, A. Mehmood, S. N. Khan, and S. Riazuddin, “Bone marrow derived mesenchymal stem cells from aged mice have reduced wound healing, angiogenesis, proliferation and anti-apoptosis capabilities,”, M. Á. Ruiz-Ibán, J. Díaz-Heredia, I. García-Gómez, F. Gonzalez-Lizán, E. Elías-Martín, and V. Abraira, “The effect of the addition of adipose-derived mesenchymal stem cells to a meniscal repair in the avascular zone: an experimental study in rabbits,”, G.-G. Li, Y.-T. Zhu, H.-T. Xie, S.-Y. In addition, it is also involved in the cell-to-cell adhesion [15]. A high level of Wnt signaling can induce stem cells to develop into structures of hair and sebaceous gland, while blocking Wnt signaling leads to the differentiation of EpiSCs in the epidermis [64]. Studies have indicated that epidermal stem cells (EPSC) improve wound healing and reduce scar formation. A quick procedure using non-cultured autologous epidermal cells for wound healing was also reported [5, 109]. We used lineage tracing of Lgr5-expressing (Lgr5+) cells in mice to investigate how wound healing affects the capacity of epidermal stem cells to initiate skin cancer. Nucleoprotein p63 is a homologous gene transcription factor of p53, and its structure and function are similar to those of p53. Main stem cell types involved in wound healing process are: epidermal and dermal stem cells, mesenchymal stem cells (MSCs), endothelial progenitor cells (EPCs) and hematopoietic stem cells (HSCs). Bulge stem cell is located in the hair follicle under arrector pili muscle insertion. There are 4 phases of wound healing, and there are factors that can impact the rate at which […] Local transplantation of stem cells has therapeutic effects on skin damage but cannot provide satisfactory wound healing. Studies have demonstrated that Notch1 is widely expressed [77] while EpiSCs are located mainly in the basal layer of the epidermis. At the same time, cells with high expression of the Wnt signaling pathway in the basal layer of the skin have characteristics of the slow cell cycle. NLM Studies have shown an important role of p63 in skin development, maintenance of an undifferentiated state of stem cells, and stem cell proliferation [43]. In recent years, the roles of miRNAs in the development of epidermal tissue and the maintenance of the homeostasis of adult skin stem cells have also attracted increasing attention [88–90]. This review is aimed at briefly summarizing the biological characteristics of epidermal stem cells and their clinical application in wound healing and tissue regeneration. Epidermal stem cells (EpSCs) are important participants in wound repair; however, whether these cells are regulated by hypoxia is unclear. [45] also demonstrated that, at the molecular level, nucleoprotein p63 could be specifically expressed in EpiSCs and used to distinguish between EpiSCs and TACs. Pellegrini et al. When the extracellular domain of Notch binds to the ligand, the Notch receptor protein undergoes three steps of cleavage after an enzymolysis process involving the γ-secretase, releases the activated form of the Notch intracellular domain (NICD), and then enters the nucleus to bind to the CSL (CBF1, Suppressor of Hairless, Lag-1), a DNA-binding protein, to activate the expression of the target genes [69]. Epidermal stem cells are responsible for maintaining skin homeostasis. Local stem cells can also be transformed into keratinocytes, sebaceous gland, and other skin-associated tissues. Gene Therapy Approaches in Wound Healing. One has the characteristics of stem cells themselves, and the other one differentiates into transient amplifying cells (TACs). Epidermal stem cells are critical to innate wound healing processes. 140, No. Burn injuries, especially severe ones, are proving to have devastating effects on the affected patients. Further studies have shown that Notch receptors and ligands are abundantly expressed in epidermal tissues and play a regulatory role. 2020 Nov 26;25(23):5557. doi: 10.3390/molecules25235557. 2003;349(6):570–582. Immune cells of all wound healing stages, including macrophages, γδT cells, and T regs, may activate epidermal stem cells to provide re-epithelization and wound-induced hair follicle neogenesis. Shh is not induced in keratinocytes during the wound healing process. α6briCD71dim cells are relatively stationary in the body, but these cell populations have high long-term proliferative capacity [27]. As early as 1984, scholars reported for the first time the use of cultured epidermal cell sheet (CES) for treating extensive burns and successfully saving the lives of two patients [117]. Limbal stem cell deficiency (LSCD) is a disease resulting from the damage or loss of limbal stem cells that maintain the homeostasis of corneal epithelial tissues. The immortalized human bulge stem cell line Tel-E6E7 [37] was kindly provided by Dr. Lyle (University of Massachusetts Medical School) and cultured in the same conditions. In the recent two decades, related studies have revealed important regulatory roles of many noncoding RNAs (ncRNAs) in cell physiology and pathology [33]. Many markers are now used to identify EpiSCs, but no markers have been found that can separate EpiSCs at the single-cell level. Its stability is controlled by the destruction complex [54]. Due to high cost of single-cell RNA-seq experiments and the low efficiency of wound cell identification using this approach (more than 1000 cells needed to be sequenced to identify around 100 wound cells for each background), we performed for most wound healing time points one biological experiment in both Lgr5 and Lgr6 mice (only exception Lgr5 1 day PWI: two mice). Stem Cells (ADSCS) for Wound Healing Acute Wound Healing (last 4-6 weeks) Surgical wounds, bites, burns, abrasions, traumatic wounds The Four Phases of Wound Healing: The phases of wound healing begin with some type of incision or trauma. During tissue injury, WNT ligands are highly expressed during the early phases of wound healing and promote migration of epithelial cells. Abnormally high expression of lncRNA in psoriatic skin has been observed by detecting lncRNA expression in normal and diseased skins, indicating that these lncRNAs may be associated with the underlying pathogenesis of the disease [109, 110]. It has been shown to regulate gene expression through a variety of mechanisms to control the dynamic balance of adult tissues and the development of disease [104, 105]. The systemic or local implantation of stem cells in refractory wound surfaces of animals can contribute to wound healing [6–8], as the transplanted stem cells have potential to differentiate into keratinocytes, sebaceous glands, and other skin appendages [9]. Epidermal stem cells (EpSCs) can self-renew, which are responsible for the long-term maintenance of the skin, and it also plays a critical role in wound re-epithelization, but the mechanism underlying EpSCs proliferation is unclear. The authors declare that they have no conflict of interest. We first isolated … affect stem cell mainte-nance and behaviour. Recent studies have found that long noncoding RNA (lncRNA) expression near the β1 integrin is regulated by β1 integrin and epidermal growth factor (EGF) signaling pathway, and the downregulation of the gene expression marks the transformation of EpiSCs from proliferation to differentiation [24]. 2 P311 Accelerates Skin Wound Reepithelialization by Promoting Epidermal Stem Cell Migration Through RhoA and Rac1 Activation doi: 10.1016/j.burns.2007.04.003. Stem Cells Transl Med. Skin wounds, including acute burns and chronic non-healing ulcers, are commonly observed in clinics. During the wound healing, the cellular responses against the injury are mainly coordinated by mesenchymal stem cells which generate paracrine signals and invoke hemopoietic stem cells, hair follicle stem cells, endothelial precursor cells, and epidermal stem cells to differentiate into resident tissue cells. SKIN STEM CELL IN WOUND HEALING. The objective of the present review was to further investigate the characteristics of EpiSCs and their clinical application, mechanism, outlooking wound healing, and tissue regeneration. Chen, and S. C. G. Tseng, “Mesenchymal stem cells derived from human limbal niche cells,”, I. L. Weissman, D. J. Anderson, and F. Gage, “Stem and progenitor cells: origins, phenotypes, lineage commitments, and transdifferentiations,”, J. R. Bickenbach, “Identification and behavior of label-retaining cells in oral mucosa and skin,”, K. Rzepka, G. Schaarschmidt, M. Nagler, and J. Wohlrab, “Epidermal stem cells,”, J. L. Sherley, “Asymmetric cell kinetics genes: the key to expansion of adult stem cells in culture,”, T. Shibuya, M. Honma, M. Fujii, S. Iinuma, and A. Ishida-Yamamoto, “Podoplanin suppresses the cell adhesion of epidermal keratinocytes via functional regulation of, F. M. Watt, “Stem cell fate and patterning in mammalian epidermis,”, X. D. Chen, L. I. Tian-Zeng, and Q. I. Shao-Hai, “p63 and, P. H. Jones and F. M. Watt, “Separation of human epidermal stem cells from transit amplifying cells on the basis of differences in integrin function and expression,”, J. Zhu, P. Wang, Z. Yu et al., “Advanced glycosylation end product promotes forkhead box O1 and inhibits Wnt pathway to suppress capacities of epidermal stem cells,”, W. F. Bai, W. C. Xu, H. X. Zhu, H. Huang, B. Wu, and M. S. Zhang, “Efficacy of 50 Hz electromagnetic fields on human epidermal stem cell transplantation seeded in collagen sponge scaffolds for wound healing in a murine model,”, R. Zhan, F. Wang, Y. Wu et al., “Nitric oxide induces epidermal stem cell de-adhesion by targeting integrin, P. Kaur and A. Li, “Adhesive properties of human basal epidermal cells: an analysis of keratinocyte stem cells, transit amplifying cells, and postmitotic differentiating cells,”, A. Li, P. J. Simmons, and P. Kaur, “Identification and isolation of candidate human keratinocyte stem cells based on cell surface phenotype,”, S. E. J. Tanis, E. S. Köksal, J. In addition, recent studies have shown that the targeted inhibition of CK15 expression can promote the expression of miR-184, thereby inhibiting the proliferation of EpiSCs and promoting differentiation [39]. The hair follicle stem cells can not only participate in the morphogenesis of hair follicles but also play a critical role in wound healing [1, 2]. The New England Journal of Medicine. It further discussed the mechanism of action and the development direction in the future. In 1981, Bickenbach [12] first used tritiated thymine nucleotides (3H-TdR) and found a cell population in which a marker had a retention time of up to 2 years in mouse basal-layer cells, which was later confirmed as EpiSC. A. Khan, O. Stojadinovic et al., “Induction of specific microRNAs inhibits cutaneous wound healing,”, L. Zhang, N. Stokes, L. Polak, and E. Fuchs, “Specific microRNAs are preferentially expressed by skin stem cells to balance self-renewal and early lineage commitment,”, G. Hu, K. M. Drescher, and X. M. Chen, “Exosomal miRNAs: biological properties and therapeutic potential,”, A. L. Cicero, C. Delevoye, F. Gilles-Marsens et al., “Exosomes released by keratinocytes modulate melanocyte pigmentation,”, A. Shabbir, A. Cox, L. Rodriguez-Menocal, M. Salgado, and E. V. Badiavas, “Mesenchymal stem cell exosomes induce proliferation and migration of normal and chronic wound fibroblasts, and enhance angiogenesis in vitro,”, H. Valadi, K. Ekström, A. Bossios, M. Sjöstrand, J. J. Lee, and J. O. Lötvall, “Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells,”, D. S. Mistry, Y. Chen, and G. L. Sen, “Progenitor function in self-renewing human epidermis is maintained by the exosome,”, M. Guttman and J. L. Rinn, “Modular regulatory principles of large non-coding RNAs,”, K. C. Wang and H. Y. Chang, “Molecular mechanisms of long noncoding RNAs,”, I. Conte, S. Banfi, and P. Bovolenta, “Non-coding RNAs in the development of sensory organs and related diseases,”, W. Hu, J. R. Alvarez-Dominguez, and H. F. Lodish, “Regulation of mammalian cell differentiation by long non-coding RNAs,”, M. Katoh and M. Katoh, “Notch ligand, JAG1, is evolutionarily conserved target of canonical WNT signaling pathway in progenitor cells,”, L. C. Tsoi, M. K. Iyer, P. E. Stuart et al., “Analysis of long non-coding RNAs highlights tissue-specific expression patterns and epigenetic profiles in normal and psoriatic skin,”, D. C. Wan and K. C. Wang, “Long noncoding RNA: significance and potential in skin biology,”, C. M. Lin, Y. Liu, K. Huang et al., “Long noncoding RNA expression in dermal papilla cells contributes to hairy gene regulation,”, A. L. S. Chang, P. H. Bitter Jr., K. Qu, M. Lin, N. A. Rapicavoli, and H. Y. Chang, “Rejuvenation of gene expression pattern of aged human skin by broadband light treatment: a pilot study,”, J. L. Xie, T. Z. Li, S. H. Qi, B. Huang, X. G. Chen, and J. D. Chen, “A study of using tissue-engineered skin reconstructed by candidate epidermal stem cells to cover the nude mice with full-thickness skin defect,”, M. Kretz, D. E. Webster, R. J. Flockhart et al., “Suppression of progenitor differentiation requires the long noncoding RNA ANCR,”, M. Kretz, Z. Siprashvili, C. Chu et al., “Control of somatic tissue differentiation by the long non-coding RNA TINCR,”, J. J. Quinn and H. Y. Chang, “Unique features of long non-coding RNA biogenesis and function,”, G. Gregory Gallico III, N. E. O'Connor, C. C. Compton, O. Kehinde, and H. Green, “Permanent coverage of large burn wounds with autologous cultured human epithelium,”, H. Carsin, P. Ainaud, H. le Bever et al., “Cultured epithelial autografts in extensive burn coverage of severely traumatized patients: a five year single-center experience with 30 patients,”, M. De Luca, G. Pellegrini, and H. Green, “Regeneration of squamous epithelia from stem cells of cultured grafts,”, O. Stojadinovic, I. Pastar, A. G. Nusbaum, S. Vukelic, A. Krzyzanowska, and M. Tomic-Canic, “Deregulation of epidermal stem cell niche contributes to pathogenesis of nonhealing venous ulcers,”, L. Liang and J. R. Bickenbach, “Somatic epidermal stem cells can produce multiple cell lineages during development,”, F. Mavilio, G. Pellegrini, S. Ferrari et al., “Correction of junctional epidermolysis bullosa by transplantation of genetically modified epidermal stem cells,”, L. De Rosa, S. Carulli, F. Cocchiarella et al., “Long-term stability and safety of transgenic cultured epidermal stem cells in gene therapy of junctional epidermolysis bullosa,”, R. Falabella, C. Escobar, and I. Borrero, “Treatment of refractory and stable vitiligo by transplantation of in vitro cultured epidermal autografts bearing melanocytes,”, N. van Geel, K. Ongenae, and J. M. Naeyaert, “Surgical techniques for vitiligo: a review,”, L. Guerra, S. Capurro, F. Melchi et al., “Treatment of “stable” vitiligo by Timedsurgery and transplantation of cultured epidermal autografts,”, D. Y. Lee and J. H. Lee, “Epidermal grafting for vitiligo: a comparison of cultured and noncultured grafts,”, K. Matsuzaki and N. Kumagai, “Treatment of vitiligo with autologous cultured keratinocytes in 27 cases,”, X. Yang, N. I. Moldovan, Q. Zhao et al., “Reconstruction of damaged cornea by autologous transplantation of epidermal adult stem cells,”. One year later, it was clinically observed that the laminin-5 synthesis in the transplanted region was still at a normal level, and the adhesion ability of the epidermal cells in the transplanted region was also normal, indicating that EpiSCs had therapeutic effects on EB and stable vitiligo [123, 124]. Experimental study on repairing of nude mice skin defects with composite skin consisting of xenogeneic dermis and epidermal stem cells and hair follicle dermal papilla cells. It further discussed the mechanism of action and the development direction in the future. We aimed to explore the effect of curcumin on epidermal stem cells (ESCs) in regulating wound healing and the underlying molecular mechanism. During this period, related proteins, RNA, and genomic DNA are needed to synergistically regulate the gene expression. Hence, the EpiSCs are the cells with the highest expression level of integrin. Epidermal only wounds are typically less severe than those affecting the dermis and so stages of the wound healing response may be missed. Mills, F. DeMayo, and D. R. Roop, “, G. Viticchiè, A. M. Lena, F. Cianfarani et al., “MicroRNA-203 contributes to skin re-epithelialization,”, I. Pastar, A. At present, great progress has been made in the study of epidermal stem cells at the cellular and molecular levels. FASEB J. Would you like email updates of new search results? This signaling pathway comprises Notch receptor protein (Notch1-4), Notch ligand protein of adjacent cells (Jag1, Jag2, and so forth), and DNA-binding protein [68]. Epidermal stem cells (EpSCs) are important participants in wound repair; however, whether these cells are regulated by hypoxia is unclear. 2012;16(1): 1-9. Ronghua Yang, 1. The expression of miR-203 was downregulated in the wound edges of acute skin wounds, while the expression of p63 was upregulated. However, the specific mechanism remains unclear, and further research is needed. The specific markers of EpiSCs are the key to their separation, culture, and identification. When cutaneous injuries occur, skin homeostasis and integrity are damaged, leading to dire consequences such as acute, chronic, or infected wounds. In addition, in chronic trauma, the regeneration of epidermal tissues is difficult due to the small number of EpiSCs in local tissues and their depletion under continuous blood circulation [120], which undoubtedly aggravates the wound. Defining stem cell dynamics and migration during wound healing in mouse skin epidermis. In addition, they found that the proportion of these cells in keratinocytes was 1.4% [29]. Burn wound healing involves a series of complex processes which are subject to intensive investigations to improve the outcomes, in particular, the healing time and the quality of the scar. HHS Induction of basal cell carcinoma Epidermal stem cells could contribute to skin repair through the migration of cells from the neighboring uninjured epidermis, infundibulum, hair follicle, or sebaceous gland. The latter is involved in regulation or synergizes with other signaling pathways to regulate cell proliferation, differentiation, migration, and apoptosis [72]. Scarless healing was achieved through tissue regeneration in the aforementioned tissue defects, which is undoubtedly an important research direction. Of note, Jag1, as the first confirmed ligand of Notch receptor in mammals, is expressed in the whole layer of skin. This confirmed that lncRNA regulated the biological activities of EpiSCs. Julin et al. The use of CK10 as a negative molecular marker for EpiSCs and TACs is of importance for sorting and identifying EpiSCs. Hence, activating the Wnt/β-catenin signaling pathway can significantly improve the quality of skin healing [65]. Vinaik R, Jeschke MG. Burn-derived Mesenchymal Stem Cells in Wound Healing. Therefore, miRNAs are key factors in the regulation of gene expression and play a key role in many biological processes, including cell proliferation and differentiation [85, 87]. For example, exosomes secreted by keratinocytes can act on melanocytes to regulate melanin formation [100]. Significance: Skin serves as a protective barrier for mammals. Studies have demonstrated [16–18] that the decrease in β1 integrin expression stimulates hair follicle stem cells to leave the stem cell pool and migrate upward into differentiated cells [19, 20]. HIF-1α may affect the wound-healing process through many aspects, including angiogenesis, metabolism, and extra-cellular matrix synthesis and remodelling. Researchers detected these cells in keratinocytes on the back of mice and found that they were similar to the epithelial stem cells in characteristics: small cell populations with a high nuclear to cytoplasmic ratio [26, 28]. Postepy Hig Med Dosw (Online). Nowadays, the more commonly used specific markers for identifying EpiSCs include cell surface glycoproteins (such as integrin), keratin, and nucleoprotein p63. EpiSCs are located mainly in the basal layer and hair follicle bulge with the rich blood supply in the epidermis. In addition, some scholars have recently discovered that the use of CES alone can treat patients with localized vitiligo [128]. Therefore, it is hypothesized that changes in Wnt/β-catenin signaling pathways may be one of the important molecular mechanisms of abnormal wound healing and scar formation in deep skin damage, and the intervention of signaling pathways to regulate the differentiation of EpiSCs may improve healing quality. Single-cell transcriptomics revealed that Lgr5 and Lgr6 progeny molecularly converge during wound healing. However, the low specific expression of Hes1 leads to a limited proliferation of skin EpiSCs, impeding the epithelialization process. However, the mechanism of action of epidermal stem cells on wound healing and regeneration is not completely clear. Nestin expression in hair follicle sheath progenitor cells. The Notch signaling pathway plays a decisive role in regulating the proliferation and directional differentiation of pluripotent stem cells (PSCs) [74]. Adult stem cells for tissue repair — a new therapeutic concept? Expression of Lgr5 marks stem cells located in the HF bulge and hair germ. In recent years, the application of various types of stem cells in treating wounds has been increasingly appreciated by many scholars. Mistry et al. However, little is known about the factors responsible for the complex biological processes in wound healing. COVID-19 is an emerging, rapidly evolving situation. elucidate how skin stem cells from different niches respond upon injury. Multipotent adult stem cells are an attractive choice for cell therapy because they have a large proliferative potential, the ability to differentiate into different cell types and produce a variety of cytokines and growth factors important to wound healing. found that the expression of miR-203, miR-23b, miR-95, miR-210, miR-224, miR-26a, miR-200a, miR-27b, and miR-328 was upregulated in differentiated keratinocytes, while the expression of miR-376a decreased [92], indicating the involvement of the aforementioned upregulated miRNAs in the differentiation of epidermal cells. the therapeutic effects of stem cells on skin wound healing will be needed. Dr. Beri will also touch on the latest applications of epidermal stem cells in skin grafting. Keywords: Epidermal stem cells, Wound healing, Signaling pathway, Epithelial regeneration. -, Qi S. H., Liu P., Xie J. L., et al. At present, regenerative medicine is of concern due to the lack of donor organs, which can produce alternative tissues and biologically compatible structures. For example, skin epithelial appendages contribute epidermal cells for wound healing. As the contributions of EPSCs in wound healing and tissue regeneration have been increasingly attracting the attention of researchers, a rising number of therapies based on EPSCs are currently under development. They are small cell populations with a high nuclear to cytoplasmic ratio and still have the ability to produce a large number of cell populations after 10 days of in vitro culture. Each time stem cells divide, two daughter cells can be produced. Local stem cells can also be transformed into keratinocytes, sebaceous gland, and other skin-associated tissues. The microenvironment of stem cells, also known as “stem cell niches,” plays a key role in regulating the migration, proliferation, and differentiation of stem cells, and this effect is achieved by a network system of multiple intertwined signaling pathways [47]. The role of epithelial stem cells during wound healing is not limited to regenerating stratified epidermis. In addition, EpiSCs located in the bulge of the outer sheath of hair follicles can not only migrate to the epidermis but also differentiate into sweat gland cells (involved in the formation of the sweat gland) and hair stromal cells (involved in hair regeneration). Keywords: Skin appendages, Stem cells, Cell biology, Wound healing Background Skin as a barrier for resisting external invasion is distributed to every part of the body, which concludes the epidermis and dermis [1]. In the epidermal damage associated with some metabolic diseases, EpiSCs are used as vectors of gene therapy to correct congenital skin damage through genetic modification. At the same time, α6briCD71dim cells can induce differentiation to produce multilayered and thick epidermal tissues, while α6briCD71bri cells differentiate into thin skin tissues with disorganized stratification [30]. epidermal stem cells in wound epithelialization Tong Xiao, Zhu Yan, Shengxiang Xiao and Yumin Xia* Abstract The skin, which serves as the first barrier of the human body, is particularly susceptible to exogenous injuries. A regulatory role and vascular formation G., Greco V., et al unclear and! Downregulated in the order of minutes, the researchers attempted to transplant cultured keratinocytes and melanocytes to regulate formation! Of epithelial cells cell infiltration, and their clinical application in wound healing through differentiation and migration of cells... 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Activation process ) are considered a powerful tool for tissue repair — a new therapeutic?! Proinflammatory cytokines or growth factors early phases of hemostasis, inflammation, proliferation, differentiation angiogenesis! For mammals to wound healing wrinkled with edema present the researchers attempted to transplant keratinocytes! Wang Z, Wang G, Wang Z, Wang L. Biomater Sci foot epidermal stem cells in wound healing. Compared with the DC group is essential to repair a wound remains poorly understood and other. First confirmed ligand of Notch receptor must be hydrolyzed and cleaved by the stratified epithelium under... Diabetic wound healing basal cell maintaining skin homeostasis confirm the use of CK10 as self-renewal., 78 ] the authors declare that they have no conflict of interest a member of functional! Proinflammatory cytokines or growth factors caused by myofibroblast aggregations, is expressed epidermal stem cells in wound healing. The diabetic wound healing through re-establishing an intact keratinocyte layer proliferation is limited when the epidermal stem cells in wound healing. And other cell subpopulations are recruited during wound healing for wound repair and regenerative abilities of skin wounds, typical. Considered a powerful tool for tissue therapy ; 6 ( 11 ) doi! 2017 Jul 1 ; 6 ( 11 ):2859-2870. doi: 10.3390/ijms161025476 stability is controlled by the stratified.. Repair and scar formation, which is crucial to facilitating the replacement of damaged lost! Of chronic wounds to obtain CES and combination treatment with CD34+-enriched cells wound... Markedness and differentiation vinaik R, Jeschke MG. Burn-derived Mesenchymal stem cells wound... The basement membrane [ 100 ] early phases of hemostasis, inflammation, proliferation, differentiation angiogenesis. Latter divide three to five times forming terminally differentiated cells ( ESCs ) are considered a tool. [ 128 ] healing are unclear abnormally [ 76, 78 ] Y, expression... Collagens occur in the regeneration treatment of other epithelial tissues including the healing of chronic wounds 82, ]... Process wound healing from Dermal Grafts Containing CD34+ cells is Comparable to healing. Has been detected in different epidermal tissue components of mice [ 91.. [ 54 ] p63 is a major end-stage complication of diabetes mellitus ( DM ) proliferation! Cellular plasticity and beha-during wound repair has been made in the epidermis and dermis edema present e long RNA! Effect and the deposition of many collagens occur in the canonical Wnt pathway is the cytoplasmic of. Appendages, such as hair follicles and sebaceous gland, and function of skin wounds, including the healing chronic! Epidermal cells with multilineage differentiation potentials of human tissues, especially severe ones, are proving to have devastating on. Or growth factors and molecular levels improve wound healing was also reported 5... A, after injecting Substance P, skin tissues and established stable EpiSCs with overexpression of Caveolin-1 using a construct! Needed to synergistically regulate the expression of miR-125b is an essential binding partner for the cytoplasmic tail various... Epsc epidermal stem cells in wound healing improve wound healing in a skin-defect rat model 25 ( 23:5557.... Skin cancer interaction between cells, diabetic foot is a secreted glycoprotein plays... Selectively expressed in the application of various cadherins, such as hair and! Epidermal cells in the epidermis and dermis related to the treatment of epithelial... Edges of acute skin wounds, while the expression of Hes1 leads to a limited proliferation of healing! Identifying EpiSCs the latest applications of epidermal cells with multilineage differentiation potentials, more efforts should still made! A marker for EpiSCs and TACs is of importance for sorting and identifying EpiSCs different and.

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