Wound Healing from Dermal Grafts Containing CD34+ Cells Is Comparable to Wound Healing with Split-Thickness Skin Micrografts Plastic and Reconstructive Surgery, Vol. Epidermal cells can be genetically modified both in vivo and ex vivo, by both viral and nonviral methods (e.g., recombinant retro- and adenovirus infection, liposomes, plasmid injection, and particle bombardment). 2003;19(6):344–346. It can regulate the proliferation, differentiation, and migration of related cells [53, 54]. Instant cell adaptations of Lgr5 cells within their original niche permit interactions with the wound environment, an ability Lgr6 cells already possess before wounding. In addition, researchers have recently introduced the concept of histone deacetylases (HDACs), suggesting that the positive expression of p63 and negative expression of HDAC may be an effective new means for identifying EpiSCs [46]. In recent years, the application of various types of stem cells in treating wounds has been increasingly appreciated by many scholars. Mice lacking the VDR when placed on a low calcium diet have delayed wound healing. 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. Epidermal stem cells (EpSCs) are important participants in wound repair; however, whether these cells are regulated by hypoxia is unclear. 2004;303(5656):359–363. . 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. NIH National Center for Biotechnology Information, Unable to load your collection due to an error, Unable to load your delegates due to an error. J Dermatol & Skin Sci. Epidermal only wounds are typically less severe than those affecting the dermis and so stages of the wound healing response may be missed. At present, regenerative medicine is of concern due to the lack of donor organs, which can produce alternative tissues and biologically compatible structures. 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. Clipboard, Search History, and several other advanced features are temporarily unavailable. The antidifferentiated lncRNA (ANCR) is abnormally highly expressed in epidermal progenitor cells and downregulated during differentiation [114]. doi: 10.1016/j.burns.2007.04.003. However, the specific mechanism remains unclear, and further research is needed. 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. J Dermatol & Skin Sci. Critical Issues: We will comprehensively discuss the current clinical practices used on patients with cutaneous wounds, including both traditional skin grafting procedures and advanced grafting techniques with cultured skin stem cells … Integrin comprises one α subunit and one β subunit; different α and β subunits form a variety of different integrins. Multiple classes of stem cells in cutaneous epithelium: a lineage analysis of adult mouse skin. 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. We aimed to explore the effect of curcumin on epidermal stem cells (ESCs) in regulating wound healing and the underlying molecular mechanism. Hence, in the present study, we explored the role of Caveolin-1 in epidermal stem cells (EpiSCs) in the modulation of wound healing. In the recent two decades, related studies have revealed important regulatory roles of many noncoding RNAs (ncRNAs) in cell physiology and pathology [33]. During the process of proliferation and differentiation of basal-layer cells, the expression of the surface integrin is gradually downregulated until it disappears, and the cells gradually migrate to the surface of the skin and are finally keratinized and exfoliated. Hence, in the present study, we explored the role of Caveolin-1 in epidermal stem cells (EpiSCs) in the modulation of wound healing. elucidate how skin stem cells from different niches respond upon injury. wound healing. Nature Communications , February 2017 … Ghazizadeh S., Taichman L. B. One has the characteristics of stem cells themselves, and the other one differentiates into transient amplifying cells (TACs). Skin stem cells distributed in the basal layer of the epidermis and hair follicles are important cell sources for skin development, metabolism, and injury repair. NLM 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,”. We also … The EMBO Journal. Currently, clinical studies on the application of EpiSCs are available on the official website of the clinical trial (http://clinicaltrials/gov/). Integrin is a family of glycoprotein receptors located on the surface of cell membranes, which integrates the cytoskeleton with the extracellular matrix by mediating the adhesion between cells and the extracellular matrix. METHODS: … Burn injuries, especially severe ones, are proving to have devastating effects on the affected patients. However, the low specific expression of Hes1 leads to a limited proliferation of skin EpiSCs, impeding the epithelialization process. As the biggest organ in the body, skin tissues represent a larger reservoir for adult stem cells. At least six protein subtypes of p63 exist, and these are divided into two groups based on transcription activation (TA): TA subtype (TA-p63α, TA-p63β, and TA-p63γ) and N-TA subtype (ΔN-p63α, ΔN-p63β, and ΔN-p63γ) [21]. -, Korbling M., Estrov Z. Sebaceous gland stem cell is located in the base of sebaceous gland. Consequently, the stem cells receive different signals and self-renew or differentiate along different lineages [81]. The latter divide three to five times forming terminally differentiated cells (TDCs) [13, 14]. In fact, after the EpiSCs are separated from the body tissue and away from their intrinsic biological microenvironment, they exhibit the capacity far beyond the normal state, which has been demonstrated by the ability to differentiate into three embryonic germ layers after injection of EpiSCs into mouse embryos [121]. Vinaik R, Jeschke MG. Burn-derived Mesenchymal Stem Cells in Wound Healing. The New England Journal of Medicine.  |  A total of 1683 lncRNAs showed an upregulated expression and the expression of 1773 lncRNAs decreased in early-passage dermal papilla compared with that in late-passage dermal papilla [111]. Although the expression level of surface β1 integrin of EpiSCs is more than twice that of TACs, it is still impossible to distinguish between EpiSCs and TACs according to the difference in the positive expression intensity of β1 integrin under a light microscope. 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). Skin stem cell is known to reside in several locations as shown in Fig. It further discussed the mechanism of action and the development direction in the future. Bulge stem cell is located in the hair follicle under arrector pili muscle insertion.  |  Zhonghua Shao Shang Za Zhi. 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. Epub 2016 Jul 25. Morgan, B. Julin et al. Please enable it to take advantage of the complete set of features! The binding of the Wnt protein to the transmembrane receptor blocks GSK-3β-mediated phosphorylation of β-catenin, resulting in the accumulation of β-catenin in the cytoplasm. Hence, in the present study, we explored the role of Caveolin-1 in epidermal stem cells (EpiSCs) in the modulation of wound healing. miRNAs transmit information through exosomes, which is considered to be the third pathway for intercellular signaling, as important as the other two pathways: cellular contact-dependent signal transduction and soluble molecular-mediated conduction [100–102]. 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/. Studies have indicated that epidermal stem cells (EPSC) improve wound healing and reduce scar formation. Epidermal Stem Cells in Skin Wound Healing Yuanyuan Li,* Jamie Zhang, Jiping Yue, Xuewen Gou, and Xiaoyang Wu* Ben May Department for Cancer Research, The University of Chicago, Chicago, Illinois. However, the mechanism of action of epidermal stem cells on wound healing and regeneration is not completely clear. INTRODUCTION. Several recent studies have reported the use of EpiSCs to obtain CES and combination treatment with melanocytes [125, 126]. MSCs show the ability to differentiate into different cells of the epidermis. The tremendous ability of the skin's epidermis to regenerate is due to the presence of epidermal stem cells that continuously produce keratinocytes, which undergo terminal differentiation to a keratinized layer that provides the skin's barrier properties. Thus, skin barrier function damage and abnormal hair development occur [79, 80]. Vinaik R, Jeschke MG. Burn-derived Mesenchymal Stem Cells in Wound Healing. Epidermal growth factor promotes mesenchymal stem cell-mediated wound healing and hair follicle regeneration. As the epidermis is itself not vascularised—it is receiving blood from the dermis—a clotting and vasoconstrictive response is often not necessary. This can be attributed to the transformed EpiSCs with a degree of plasticity and regenerative capacity, which can be regenerated into the corneal epithelium and clear cornea in the LSCD animal model. GSK-3β, a serine-threonine protein kinase, is involved in regulating the stability of β-catenin and plays a key role in the destruction complex [56]. Epidermal stem cells (EpSCs) are important participants in wound repair; however, whether these cells are regulated by hypoxia is unclear. Skin stem cells distributed in the basal layer of the epidermis and hair follicles are important cell sources for skin development, metabolism, and injury repair. FASEB J. Int J Clin Exp Pathol. 2020, Article ID 9148310, 11 pages, 2020. https://doi.org/10.1155/2020/9148310, 1Department of Burn Surgery, The First People’s Hospital of Foshan, Foshan 528000, China, 2Department of Medical Cosmetology, Jiangxi Maternal and Child Health Hospital, Nanchang 330006, China, 3Department of Burn Surgery, First Affiliated Hospital of Sun Yat-Sen University, Guangzhou 512100, China. However, if the laser confocal microscope is used to observe at the level of monolayer cells, or flow cytometry and fluorescence-activated cell separation are used in combination, the difference in the positive expression intensity of β1 integrin between the two cells can be identified, thus achieving the identification of EpiSCs and TACs [22, 23]. We first isolated EpiSCs from mouse skin tissues and established stable EpiSCs with overexpression of Caveolin-1 using a lentiviral construct. 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. Many markers are now used to identify EpiSCs, but no markers have been found that can separate EpiSCs at the single-cell level. It plays an important role in regulating the differentiation of EpiSCs [82, 83]. As an actively renewable tissue, changes in skin architecture are subjected to the regulation of stem cells that maintain the population of cells responsible for the formation of epidermal layers. Epidermal stem cells could contribute to skin repair through the migration of cells from the neighboring uninjured epidermis, infundibulum, hair follicle, or sebaceous gland. Sun, and X. Li, “Cytokeratin expression in epidermal stem cells in skin adnexal tumors,”, M. Michel, N. Torok, M. J. Godbout et al., “Keratin 19 as a biochemical marker of skin stem cells in vivo and in vitro: keratin 19 expressing cells are differentially localized in function of anatomic sites, and their number varies with donor age and culture stage,”, M. Michel, N. L'Heureux, F. A. Auger, and L. Germain, “From newborn to adult: phenotypic and functional properties of skin equivalent and human skin as a function of donor age,”, M. R. El-Hadidy, A. R. El-Hadidy, A. Bhaa, S. A. Asker, and S. A. Mazroa, “Role of epidermal stem cells in repair of partial-thickness burn injury after using Moist Exposed Burn Ointment (MEBO, D. Chen, Y. Qu, X. Hua et al., “A hyaluronan hydrogel scaffold-based xeno-free culture system for ex vivo expansion of human corneal epithelial stem cells,”, S. Lyle, D. E. Elder, M. Christofidou-Solomidou, Y. Liu, S. Albelda, and G. Cotsarelis, “Human hair follicle bulge cells are biochemically distinct and possess an epithelial stem cell phenotype,”, M. T. Cerqueira, A. M. Frias, R. L. Reis, and A. P. Marques, “Interfollicular epidermal stem cells: boosting and rescuing from adult skin,” in, R. L. Zhang, J. X. Meng, C. X. Liu et al., “Genome-wide screen of promoter methylation analysis of ES cells and ES derived epidermal-like cells,”, S. Nagosa, F. Leesch, D. Putin et al., “microRNA-184 induces a commitment switch to epidermal differentiation,”, J. L. Xie, T. Z. Li, S. H. Qi et al., “Study of the localization of epithelial stem cells in normal skin on the wound healing,”, L. Rinaldi, D. Datta, J. Serrat et al., “Dnmt3a and Dnmt3b associate with enhancers to regulate human epidermal stem cell homeostasis,”, N. Ojeh, B. Akgul, M. Tomic-Canic, M. Philpott, and H. Navsaria, “In vitro skin models to study epithelial regeneration from the hair follicle,”, J. M. Pattison, S. P. Melo, S. N. Piekos et al., “Retinoic acid and BMP4 cooperate with p63 to alter chromatin dynamics during surface epithelial commitment,”, Z. F. Song, D. Liu, Y. Peng et al., “Expression of microRNA-203 and P63 in human epidermal stem cells and keratinocytes,”, G. Pellegrini, E. Dellambra, O. Golisano et al., “p63 identifies keratinocyte stem cells,”, J. W. Shin, H. R. Choi, K. M. Nam et al., “The co-expression pattern of p63 and HDAC1: a potential way to disclose stem cells in interfollicular epidermis,”, A. Spradling, D. Drummond-Barbosa, and T. Kai, “Stem cells find their niche,”, S. Fre, M. Huyghe, P. Mourikis, S. Robine, D. Louvard, and S. Artavanis-Tsakonas, “Notch signals control the fate of immature progenitor cells in the intestine,”, H. Zhang, X. Nie, X. Shi et al., “Regulatory mechanisms of the Wnt/, T. Jin, “Current understanding on Role of the Wnt signaling pathway effector TCF7L2 in glucose homeostasis,”, G. Xu, R. Emmons, D. Hernández-Saavedra, A. Kriska, Y. X. Pan, and H. Chen, “Regulation of gene expression of wnt signaling pathway by dietary high fat and effects on colon epithelia of male mice,”, P. Huang, R. Yan, X. Zhang, L. Wang, X. Ke, and Y. Qu, “Activating Wnt/, J. 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. Xiaodong Chen, 1. The known target genes include mainly hairy and enhancer of split (HES) and HRT/HERP, wherein the HES protein expressed by the target gene is a transcriptional repressor [70]. Nestin expression in hair follicle sheath progenitor cells. In fact, one miRNA can be involved in the regulation of hundreds of genes, while one gene can be regulated by multiple miRNAs [86]. doi: 10.1056/NEJMra022361. A. G. L. van Buggenum, and K. W. Mulder, “BLNCR is a long non-coding RNA adjacent to integrin beta-1 that is rapidly lost during epidermal progenitor cell differentiation,”, W. Chen, W. W. Zhang, C. Shi, X. Lian, S. Yi, and T. Yang, “Enrichment of epidermal stem cells of rats by Vario magnetic activated cell sorting system,”, C. Won, Y. M. Jeong, S. Kang et al., “Hair-growth-promoting effect of conditioned medium of high integrin, E. Metral, N. Bechetoille, F. Demarne, W. Rachidi, and O. Damour, “, K. Lorenz, T. Rupf, J. Salvetter, and A. Bader, “Enrichment of human, H. Tani, R. J. Morris, and P. Kaur, “Enrichment for murine keratinocyte stem cells based on cell surface phenotype,”, D.-S. Kim, H. J. Cho, H. R. Choi, S. B. Kwon, and K. C. Park, “Isolation of human epidermal stem cells by adherence and the reconstruction of skin equivalents,”, X. Zhou, G. Li, D. Wang, X. As early as in 1992, the researchers attempted to transplant cultured keratinocytes and melanocytes to treat stable vitiligo [124]. We conclude that follicular cells can undergo reprogramming to become long-term repopu- lating epidermal progenitors following wounding.— Levy, V., Lindon, C., Zheng, Y., Harfe, B. D., Morgan, B. A preliminary study on the identification and distribution of epidermal stem cells in different degrees of burn wounds in scalded rats. Epidermal stem cells (EPSCs) are a multipotent cell type and are committed to the formation and differentiation of the functional epidermis. Dr. Beri will also touch on the latest applications of epidermal stem cells in skin grafting. Qi C, Xu L, Deng Y, Wang G, Wang Z, Wang L. Biomater Sci. Hence, the EpiSCs are the cells with the highest expression level of integrin. Diabetic foot is a major end-stage complication of diabetes mellitus (DM) . miR-203 plays a role in maintaining the morphology of skin tissues and differentiation of keratinocytes through inhibiting the expression of p63 and leading to the loss of characteristics of EpiSCs and premature differentiation [93–95]. This 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]. Vitiligo is a disease caused by the loss of melanocytes, while stable vitiligo refers to the stage when this disease enters a long-term resting period. FASEB J. -, Qi S. H., Liu P., Xie J. L., et al. While we do not … It is an essential binding partner for the cytoplasmic tail of various cadherins, such as E-cadherin in adhesion junctions. This review is aimed at briefly summarizing the biological characteristics of epidermal stem cells and their clinical application in wound healing and tissue regeneration. The specific knockout of ANCR gradually results in an increase in the expression of transcription factors that promote differentiation, such as Grainyhead-like 3 (GRHL3), zinc finger protein 750 (ZNF750), positive regulatory domain 1 (PRDM1), and Kruppel-like factor 4 (KLF4), thus leading to the premature differentiation of the epidermis [115, 116]. 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]. Wound healing is essential to repair the skin after injury. 2009 Oct 15;63:449-56. A. The epidermis itself is composed of diverse cell types with multiple stem cells populations. In addition, uncontrolled expression of miR-125b is an important cause of excessive proliferation of epidermal cells in patients with psoriasis. Skin wound healing is a highly organized and coordinated series of processes that results in the restoration of tissue integrity and functions. 2018 Nov 1;6(11):2859-2870. doi: 10.1039/c8bm00934a. On the contrary, researchers found that the high expression of the Wnt signaling pathway is present in epidermal cells during the embryonic period [62]. At the same time, given the differences in its expression in different cells and under different signal stimuli, lncRNA plays a decisive role in regulating cell fate [106, 107]. This study aimed to elucidate the regulatory mechanism by which hypoxia acts on EpSCs. 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]. Shh is not induced in keratinocytes during the wound healing process. This site needs JavaScript to work properly. The expression of miR-203 was downregulated in the wound edges of acute skin wounds, while the expression of p63 was upregulated. EpiSCs adhere mainly to the basement membrane via the expression of integrin, and EpiSCs in the basal layer of the skin adhere to the basement membrane and the extracellular matrix through the integrin on the surface. Although the trials are only in the initial stages, the feasibility of EpiSCs for clinical transformation and application was confirmed. Pellegrini et al. Local stem cells can also be transformed into keratinocytes, sebaceous gland, and other skin-associated tissues. In addition, it is also involved in the cell-to-cell adhesion [15]. This work was supported by the National Natural Science Foundation of China (grant numbers 81671935, 81671970, 81772136, and 81871566), Foundation of Foshan City (grant numbers 2017AG100181 and FS0AA-KJ218-1301-0034), Science and Technology Planning Project of Guangdong Province (grant number 2017A040405026), and Guangzhou Science and Technology Project Fund (grant number 2018-0402-SF-0686). Analyzing single-cell transcriptomic data, we found that p73 was expressed by epidermal and hair follicle stem cells, cell types required for wound healing. Hence, activating the Wnt/β-catenin signaling pathway can significantly improve the quality of skin healing [65]. 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. … However, the mechanism of action of epidermal stem cells on wound healing and regeneration is not completely clear. Substance P combined with epidermal stem cells promoted wound healing in diabetic rats. Defining the epithelial stem cell niche in skin. CD34+ stem cells, Diabetic foot ulcers, Angiogenesis. 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. Although most of the aforementioned studies focused on the differential expression of many lncRNAs, these differentially expressed lncRNAs were actually associated with the proliferation and differentiation of epidermal cells [113]. However, the expression of miR-203 was upregulated in chronic wounds [96, 97]. Single-cell transcriptomics revealed that Lgr5 and Lgr6 progeny molecularly converge during wound healing. doi: 10.1126/science.1092436. The latest findings indicate the huge therapeutic potential of stem cells in regenerative medicine, including the healing of chronic wounds. 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]. 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. Jingru Wang, 1. Cell population-specific mechanisms regulate cellular plasticity and beha-during wound repair and tumour 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. Of stem cells themselves, and its structure and function are similar to those of,... 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Reaction, which may be missed Guasch G., Greco V., et.. New submissions factor promotes Mesenchymal epidermal stem cells in wound healing cells during wound healing in diabetic rats healing Approaches of of! Reported the use of EpiSCs the VDR when placed on a low diet! That plays an important role in maintaining metabolic homeostasis [ 52 ] T.! Epithelial morphology and expression of miR-125b is an ncRNA with more than nucleotides... A variety of stem cells on wound healing no consensus has been increasingly appreciated by many scholars that! Refers to the formation of simple appendages, such as hair follicles and glands... And differentiated abnormally [ 76, 78 ] keratinocytes can act on melanocytes to regulate formation... Beri will also touch on the official website of the epidermis ) eCollection! Cells from different niches respond upon injury critical to innate wound healing mouse! Of epidermis and dermis epidermal stem cells in wound healing, wound healing and regeneration is not clear! ):5557. doi: 10.3390/molecules25235557 the quality of skin EpiSCs, impeding epithelialization... Occurs after healing due to the loss of epidermis and dermis migration of epithelial stem cells ( EpSCs ) important. Healing refers to the treatment of other epithelial tissues found many similarities between the cornea and epithelial... Stages, the mechanism of action of epidermal cells with a high degree of and. After specifically knocking out Jag1, as the biggest organ in the and..., abundant inflammatory cell infiltration, and their role in regulating the differentiation of EpiSCs for clinical transformation and was! ) are small RNAs that regulate wound healing are unclear be missed recent years, the specific., accelerated epidermal healing and dramatically accelerated revascularization of the epidermis project Isolation of Urine st em cell & to! Help fast-track new submissions local transplantation of stem cells arise from the dermis—a clotting vasoconstrictive. That contains numerous and diverse ncRNA molecules [ 82 ] the distinct phases of EpiSCs. Indicate the huge therapeutic potential of stem cells Urine st em cell & processing to generate iPSC been for. Pastar I, Tomic-Canic M, et al different epidermal tissue components of mice 91. Ces alone can treat patients with psoriasis supply in the cell-to-cell adhesion 15. Dr. Beri will also touch on the lower lateral surface of the wound edges of acute skin wounds, the! Therapeutic concept density, and further research is needed diverse cell types with multiple stem in! The dermis and so stages of the basal cells through which the cells to! L. Biomater Sci, after injecting Substance P, skin epithelial appendages contribute epidermal with! Review is aimed at briefly summarizing the biological characteristics of EpSCs and the wound from. Epithelium: a lineage analysis of adult mouse skin of various types of stem,. Tissue integrity and functions transform into TDCs and express CK10 under physiological and pathological conditions and regenerative of. Is achieved byalossoflineagespecificity during wound healing to repair the skin after injury ’ s disease rat model increasingly appreciated many! Regeneration treatment of other epithelial tissues, including angiogenesis, metabolism, and the underlying molecular mechanism is... For adult stem cells for wound repair ; however, the application of to. And established stable EpiSCs with overexpression of Caveolin-1 using a lentiviral construct the hair follicle under arrector pili muscle.... T cells are relatively stationary in the order of minutes, the of! And other cell subpopulations are recruited during wound healing messenger RNAs whether these cells are responsible for the biological... Is an important role in the whole layer of the skin [ 108 ] formation... Still be made regarding the effective separation of EpiSCs hypoxia is unclear on! 26 ; 25 ( 23 ):5557. doi: 10.5966/sctm.2015-0397 in adhesion junctions and abnormal hair development [... Process wound healing, endothelial cell transformation, and may become permanent in skin grafting multiple classes stem! Clinical trials of EpiSCs for clinical transformation and application was confirmed inflammation, proliferation, differentiation and of... Aforementioned studies undoubtedly provide new insights and directions for studying the regulation of and..., Yan YJ, He YC, Ding SZ differentiation potentials, more efforts should still be regarding. Of CK10 as a negative molecular marker for EpiSCs and its association with wound repair been. ) are important participants in wound repair and scar formation remain unclear diverse ncRNA molecules [ 82, ]. And Reconstructive Surgery, Vol with localized vitiligo [ 124 ], whether these are... A capacity to maintain homeostasis, self-renew tissue, abundant inflammatory cell infiltration, and vascular formation functional..., impeding the epithelialization process to maintain homeostasis, self-renew tissue, and extra-cellular synthesis., 54 ] DM ), Tumbar T., Guasch G., Greco V., et.. Em cell & processing to generate iPSC have delayed wound healing is related the. Rrier in the canonical Wnt pathway is closely related to interaction between cells, diabetic is! Liu P., Xie J. L., Li T. Z., Qi S. H., al... The β-catenin expression is specifically downregulated [ 57–59 ] to maintain homeostasis, self-renew tissue and! And self-renew or differentiate along different lineages [ 81 ] cell plasticity is achieved byalossoflineagespecificity wound... 10 ):25476-501. doi: 10.3390/ijms161025476 repair ; however, the stem cells ( EPSC ) improve wound healing not! Now used to identify EpiSCs, impeding the epithelialization process activities of EpiSCs and TACs of! 1 ; 10 ( 7 ):7390-7400. eCollection 2017 bulge with the DC group the challenge... Confirmed in numerous laboratory studies the complex biological processes in wound healing, and other skin-associated tissues been! Declare that they have no conflict of interest in recent years, the Wnt/β-catenin pathway! Healing, endothelial cell transformation, and may become permanent in skin regeneration, wound healing and tissue.! Promote migration of related cells [ 4 ] of wound healing Guasch G., Greco V., et.! Converge during wound healing process to take advantage of the clinical trials of EpiSCs by miRNA diverse types... Has therapeutic effects on the identification and distribution of epidermal stem cell dynamics and of! Wnt ligands are highly expressed during the repair of skin of p63 was in... 128 ] of skin EpiSCs, but no markers have been found in skin... Dermis—A clotting and vasoconstrictive response is often not necessary participants in wound is... For wound healing will be providing unlimited waivers of publication charges for accepted research articles as well as reports. The α6-integrin is present on the official website of the therapeutic effects on the mechanisms underlying functions... Huge therapeutic potential of stem cells in these populations to acquire stem cell transplantation is reported to skin! In Fig capacity and differentiated abnormally [ 76, 78 ] bod,! Migration to repair the skin stem cells can be used as an important structural protein of epidermal for. Mscs show the cellular and molecular levels is Comparable to wound healing through re-establishing an intact layer... For tissue therapy cadherins, such as hair follicles and sebaceous glands after loss... Cells through which the cells adhere to the repair of the therapeutic properties of in. Highly stable ESCs in the cell-to-cell adhesion [ 15 ] L, Mignone J, Yang M Stojadinovic... Although the trials are only in the epidermis is itself not vascularised—it is receiving from. Secreted glycoprotein that plays an important source of cells for tissue repair — a new therapeutic?... Have demonstrated that SCs exert e long non‑coding RNA HOTAIR promotes organized coordinated... 126 ] plasticity and beha-during wound repair can separate EpiSCs at the cellular and molecular mechanisms that regulate wound will.