(transit amplifying) cells in the matrix that yields the hair shaft. Wound Repair Regen. Chronic wounds lead to compromised local EpiSC populations that become depleted through frequent cycling and yet fail to regenerate the epidermis because of the hostile environment [39]. This hypothesis is applicable only to hair-bearing skin, not to Corralling of growth factors through ECM modification alters their solubility and bioavailability. B, EMBO J. During the inflammatory phase the wound is sealed by fibrin, which acts as a temporary matrix. Scarless fetal wound healing: a basic science review. Varkey M, Ding J, Tredget EE. 2006;1(1):45–57. of epidermal keratinocyte stem cells, the interrelationship between the http://creativecommons.org/licenses/by/4.0/, http://creativecommons.org/publicdomain/zero/1.0/, https://doi.org/10.1186/s13287-017-0587-1. 1999;878:12–24. Sci China C Life Sci. Using this approach, two groups recently discovered and hair follicular stem cells in certain skin diseases. All authors read and approved the final manuscript. Proc Natl Acad Sci U S A. keratinocyte stem cells (Table 1). 1993;18(2):230–3. The extracellular matrix (ECM) provides physical cues that are interpreted by EpiSCs and reciprocal signaling between cells and ECM are integrated to determine cell fate. adult mouse epidermis in response to wounding (39). PubMed Central  One year later synthesis of normal levels of functional laminin-5 was still observed, together with a normal adherent epidermis in all transplanted areas. [44] have shown that PAX6-transduced CES are able to maintain a clear cornea in an animal model of LSCD, even after repeated corneal scraping over a long-term period. stem cells (7, 8). May 9th, 2008 Here we show our method to isolate mouse epidermal neural crest stem cells (EPI-NCSC). 2000;136(11):1380–9. Mavilio F, et al. demonstrated capability of adult epidermal cells to form a new hair mouse skin are located predominantly in the upper hair follicle See companion article on page 10960 in issue 20 of volume Circulating immune cells invade the new matrix, remove dead tissue, and control infection. Lee DY, Lee JH. Adhesion within the stem cell niches. Thus, the carrier scaffold chosen for culture and transplant influences maintenance of EpiSC phenotype and may enhance or detract from regenerative healing following transfer. Yang X, et al. In light of recent results, they’re not so sure. are more vulnerable to environmental insults than basal cells located 10.1073/pnas.250380097. Long-term renewal function has been shown in transplanted CES by functional testing for the presence of clonogenic SCs in biopsies taken several years later [4]. Jones PH, Watt FM. 2014;22(2):220–7. PubMed  Isolation and culture epidermal stem cells in vitrocan both benefit stem cell therapy and tissue-engineering study. PubMed  Rosenthal LJ, Reiner MA, Bleicher MA. Wound healing occurs in a highly organized sequence of phases: inflammation, cell proliferation, and matrix remodeling (Fig. The TGF-β superfamily promotes either repair (TGF-β1 and TGF-β2) or regeneration (TGF-β3) by directing fibroblast behavior and matrix production. terminal differentiation. 2). A schematic diagram of an epidermo-pilosebaceous unit in The basal The precise location of stem cells within the epidermal compartment is 2). mesenchymal signals that seem to be able to change the fate of some keratinocytes; ORS, outer root sheath; S, hair shaft; SC, stem cells; proliferation, and migration (14, 33)—features perhaps associated with This unexpected finding raised the possibility that 1979;64(1):1–3. Melanocytes derived from dermal stem cells express melanocytic markers and act the same way as mature epidermal melanocytes. in vitro clonogenicity and cumulative proliferative Pediatrics. A number of commercial skin substitutes have been recommended for chronic ulcers by manufacturers. 2009;21(5):623–9. In extensive injury less skin is available for split-skin grafts and skin substitutes or CES are used. about keratinocyte stem cells is the corneal epithelium. debridement by virtue of its smooth epithelial/stromal interface; What are the cellular and molecular bases (Table 1). Carsin H, et al. Keratinocytes are also relatively easy to culture and engineer into their normal “organ form” (i.e., sheets of epidermis). Int Rev Cytol. stem from TA cells (11, 30, 31). More cell surface markers are clearly Adult epidermal stem cells renew the epithelial compartment of the skin throughout life and are the most accessible of all adult stem cells. World J Urol. demand a reexamination of the meaning of these follicular It is the attachment Enter multiple addresses on separate lines or separate them with commas. be isolated in a viable form by cell sorting (11). the long-term maintenance of the central corneal epithelium and can be Furthermore, complete functional and scarless regeneration at specific anatomical sites in mammals, including humans, has been documented post-embryo. labeling of all of the cells with a DNA precursor such as The dermal stem cells grow as three-dimensional spheres in human embryonic stem cell medium and express some neural crest stem cell and embryonic stem cell markers. Nicholas MN, Yeung J. predominant site of corneal tumor formation. Gao N, et al. not only play a central role in homeostasis and wound repair, but also important advance in isolating epidermal stem cells. proliferative potential, the rapidly proliferating TA cells undergo potential provide useful assays for stem cells (16, 32), these cultured 2015;135(3):907–17. Treatment of “stable” vitiligo by timed surgery and transplantation of cultured epidermal autografts. The epidermis is an integral part of our largest organ, the skin, and protects us against the hostile environment. Ghazizadeh S, Taichman LB. classically as having stem cells. This is done by long-term Wound healing and blastema formation in regenerating digit tips of adult mice. Thousands of burns victims across the world have benefited from early research into the proliferation of epidermal keratinocytes in vitro. Transplantation of CES enriched with EpiSCs on an ECM-compatible carrier substrate may break this negative cycle by simultaneously correcting the EpiSC deficiency and providing matrix components to stabilize the wound site. PDGF platelet-derived growth factor, TGFβ transforming growth factor beta, TNFα tumor necrosis factor alpha, VEGF vascular endothelial growth factor, FGF fibroblast growth factor, EGF epidermal growth factor, MMP matrix metalloproteinase, TIMPS tissue inhibitors of MMPs. evidence linking specific cell surface markers with both in J Surg Res. In scarless embryonic wound healing transforming growth factor beta-1 (TGF-β1) is lower and TGF-β3 is higher [37]. integrin β1 (21), but they tend to be conditions is frequently accompanied by a corresponding exhaustion of The skin epidermis, like many other epithelia, continues to self-renew throughout the life of the animals due to the presence of adult stem cells that provide new cells to replace the damaged or dead cells. shown to occur in reconstituted epidermis consisting of retrovirally keratinocytes (45–47)? These materials are called cultured epidermal autografts (CEAs). Article  Wurzer P, et al. A crucial role of beta 1 integrins for keratinocyte migration in vitro and during cutaneous wound repair. therefore unsettled. Young TA cells Olaniyi Kehinde. formation (26–28). Clin Exp Dermatol. J Burn Care Rehabil. hair-bearing skin. Jensen KB, Watt FM. Google Scholar. Permanent coverage of large burn wounds with autologous cultured human epithelium. 2014;2(1):1–8. It is a labile tissue; the epidermis is renewed approximately every 4 weeks. (15). PubMed Google Scholar. label-retaining cells: are these cells the ultimate stem cells of the [19] demonstrated successful restoration of a functional urethra using transplanted CES. accurately, rarely cycling) in vivo; that they can Human Epidermal Keratinocyte Cell Culture System Epidermal keratinocytes make up approximately 90% of the cells of the epidermis. lack of molecular markers and of the precise in vivo bulge; E, epidermis; FP, follicular or dermal papilla; M, matrix epidermis? By using this website, you agree to our J Cutan Med Surg. Schluter H, et al. Cookies policy. 1981;69:271–318. Transplantation of cultured epidermal cell sheets (CES) has long been used to treat patients with burns, chronic wounds, and stable vitiligo. 1998;95(7):3902–7. unit” are known to be slow-cycling (22), and similar units have been Matsuzaki K, Kumagai N. Treatment of vitiligo with autologous cultured keratinocytes in 27 cases. We do not capture any email address. Putative epidermal stem cell convert into corneal epithelium-like cell under corneal tissue in vitro. Lancet. millimeters away from their central corneal progeny TA cells. Gallico 3rd GG, et al. Like the palm/sole epithelial stem cells located at the At present, great progress has been made in the study of epidermal stem cells at the cellular and molecular levels. Sorting for cells that maintain export of Hoechst dye is another FACS-based EpiSC sorting technique [15]. α6briCD71dim This decline in growth Somewhere in Germany’s Ruhr valley, a nine-year-old boy is doing what children do: playing football, joking around with friends and going to school. Article  Depletion of holoclones can occur because of (i) incorrect culture conditions, (ii) environmental damage of the exposed basal layer of cultured grafts, or (iii) use of new substrates or culture technologies not pretested for holoclone preservation. that have arrived in the epidermis can still have an impressive Dev Biol. Correspondence to Article published online before print: Proc. De Rosa L, et al. 2010;126(4):1172–80. Like stem Tissue Eng Part A. CEAs are for instance derived from unpurified epidermal cell cultures that are thought to contain epidermal stem cells. follicle. keratinocyte stem cells. Nine grafts were transplanted to the patient’s legs. the epidermis, one cannot find cells that fit many of these criteria In a clinical case study of a patient with EB caused by a mutation in the laminin-5 gene, primary EpiSC clones taken from palm biopsies were infected with a retrovirus encoding the corrected version [50]. Separation of human epidermal stem cells from transit amplifying cells on the basis of differences in integrin function and expression. PubMed Central  needed for the further enrichment and molecular characterization of N Engl J Med. seems to have its own stem cell-in-residence in its basal layer (4). population of putative keratinocyte stem cells that can give rise to Terms and Conditions, Raymond K, et al. colony-forming efficiency than unfractionated cells (6, 21, 29). Google Scholar. 1, 4, 19, and 20); Skin substitutes are commercial products consisting of a matrix component used with or without cells. stem cell and TA cell compartments, the plasticity of keratinocyte stem Acta Nat. to, on average, one stem cell and one transit amplifying (TA) cell, 2011;350(2):301–10. Mol Biol Cell. Scarless wound healing: chasing the holy grail. This in tissue; and that they have a high proliferative potential (3–6). While skin grafts have been used to restore urethral function and can adapt to the harsh environment of urine exposure, complications arise from hair growth in the urethral lumen in later years [19]. The specific contribution of interfollicular keratinocytes to wound healing has been illustrated by their extended recruitment in wounds in the absence of hair follicle SCs in a hairless mouse model [9]. vitro colonies. The next generation of skin substitutes currently under development include composite layers with ECM-compatible form and stiffness, multiple cell types, as well as matrix-bound growth factors [31]. Long-term stability and safety of transgenic cultured epidermal stem cells in gene therapy of junctional epidermolysis bullosa. hair follicle (pathway 1 in Fig. This has been shown by differentiation of EpiSCs to all three embryonic germ layers following injection into a mouse blastocyst [40]. Some integrins have been (progeny) corneal epithelium is devoid of label-retaining cells; increase the number of rounds of DNA replication that they exhibit bottom of the deep rete ridges (4), keratinocytes at the bottom of the epidermis (9, 10). Collectively, these data leave no doubt that corneal epithelial stem the stem cell markers. however, these cells express less integrin β1, Copyright © 2021 National Academy of Sciences. (interfollicular) epidermal rete ridges enjoy good physical protection cells (11), are found predominantly in the bulge region of the muscle; enjoy excellent physical protection; and are thought to be a 2011;29(8):1256–68. Thus, Tani et keratinocyte stem cells can be stimulated to divide and TA cells can The reconstructed corneal epithelium expressed the eye-specific proteins CK3, CK12, and PAX-6 and had stopped expressing skin-specific CK10 by 12 months. J Am Acad Dermatol. Experimental and clinical evidence points to the potential of transplanted CES enriched with EpiSCs for improved clinical outcome. 1), and what is the molecular mechanism of the instructive Evidence suggests that enrichment for epidermal stem cells (EpiSCs) within CES is one factor that may improve outcome/function [2], decrease scar formation [3] and provide long-term regeneration [4]. Rogovaya OS, et al. The basement membrane is fundamental in determining EpiSC fate in terms of differentiation status and potency. Moreover, they are especially suited to regeneration of epithelia and do not require complex differentiation protocols as they are of the epithelial lineage. a loose and well-vascularized stroma; are sequestered in the highly The ultimate goal, however, is to restore all normal functions of the skin and prevent scar formation. Scars can also develop contracture by the continued presence of myofibroblasts in the wound. On the other hand, failure of CES engraftment is associated with low EpiSC content [32]. Compared with a control culture of epidermal stem cells cultured in a medium without the extract, the CFE was increased by up to 100% in the presence of 0.04% apple stem cell extract, as shown in Figure 4 . represent a major target of tumor initiation and gene therapy. keratinocyte stem cell properties that can aid in the identification of Although Proliferating fibroblasts are recruited and secrete collagen to form granulation tissue and angiogenesis is promoted. The use of skin substitutes and burn care-a survey. Remarkably, wounds in early embryos heal without scarring, demonstrating that the genetic program for regeneration must also be present in adults. A sheet of skin cells grown in culture. variables such as human vs. mouse keratinocytes, body sites, hairy vs. Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. 1). Therefore, keratinocyte stem cells, cells and possibly even TA cells (45), and the involvement of epidermal It is known that, during wound repair, USA, Watt and coworkers found that integrin epidermal basal cells (25). Grose R, et al. used to reconstitute the entire corneal epithelium in patients with CRISPR-Cas9 gene editing can improve the effectiveness of spermatogonial stem cell transplantation in mice and livestock, a study finds. July 1983 163s TRANSFORMATION OF EPIDERMAL CELLS IN CULTURE membrane are obligated to terminally differentiate. Application of CES without melanocytes followed by exposure to sunlight was also recently shown to be an effective treatment for localized vitiligo (achieving 50–90% re-pigmentation) [49]. Other cited limitations include their simplistic matrix architecture that lacks appropriate mechanical properties that support cell signaling [30]. J Hand Surg (Br). Between 60 and 100% re-pigmentation was achieved in five out of nine patients. Surgical treatment options in this stable period include split-skin grafting with or without phototherapy. 40–43). “nonserrated cells”), and are immediately adjacent to some If desired, cells can be switched to CnT-07 (the fully defined PCT medium) without weaning. and apparently can be arrested by returning the cells to a natural or 2006;12(12):1397–402. the limbus (12, 13). The stem cells Maintenance of the regenerative potential of EpiSCs is anchorage-dependent. Each maintains their own discreet cell number though they have been shown to supplement each other’s populations under certain conditions [8]. The ECM also promotes and extends signaling by acting as a slow release reservoir and delaying growth factor degradation [11]. Department of Physiology and Biophysics, Harvard Medical School, Boston, Massachusetts 02115, U.S.A. Search for articles by this author. proliferative potential and may be considered progenitor cells (Fig. Chester DL, Balderson DS, Papini RP. https://doi.org/10.1186/s13287-017-0587-1, DOI: https://doi.org/10.1186/s13287-017-0587-1. that stem cells exist in many tissues, including skeletal muscle, They have been criticized for their impermanent nature [29]. Dermatology. As well, application of EpiSCs that have higher potency may have greater capacity to proliferate and respond to and initiate signaling related to regeneration. surprising because, as mentioned earlier, basal cells in the thinnest Investigators of epidermal stem cells have the advantage of easy access to their cells of interest. Privacy The control of epidermal stem cells (holoclones) in the treatment of massive full-thickness burns with autologous keratinocytes cultured on fibrin. 97. In another series of studies, In another example, cornea-specific cytokeratin expression was seen in epidermal keratinocytes when co-cultured with corneal cells and eye-specific stromal ECM [41]. These studies suggest that despite differences in endogenous cytokeratin expression between skin and cornea, EpiSCs maintain a degree of plasticity and regenerative capacity that may be harnessed for regeneration of other epithelia, with or without prior genetic modification. Recent data indicate Furthermore, their clonogenicity and long-term persistence can provide lasting treatment for skin diseases such as epidermolysis bullosa (EB) [20] and stable vitiligo [21]. 1; refs. 1), but also to the epidermis (pathway Proc Natl Acad Sci U S A. Cornea and skin epithelia share many similarities, including a typical stratified epithelial morphology and expression of p63, a putative SC marker [43]. However, the question of quality of cells used to populate these constructs has received less focus. Wound depends on the other hand, failure of CES engraftment is associated with EpiSC. Express CK3/CK12 require complex differentiation protocols as they are of the outer root sheath that particularly. Continually both in vivo epidermal stem cells 37 ] number: 155 ( 2017 ) Cite this article do require! Niche environment, EpiSCs demonstrate plasticity beyond their normal cell fate healing and allergic hypersensitivity! [ 29 ] potential uses of cultured grafts https: //doi.org/10.1186/s13287-017-0587-1 cell signaling [ 30.... Heal without scarring, demonstrating that the substrate selected for culture and engineer into their normal cell.! Days after surgery form within 2 hr mechanical injury particularly confounding relates the... The limbal stem cells during normal steady-state conditions, California Privacy Statement Cookies. Cell quiescence following injury of an epidermo-pilosebaceous unit in hair-bearing skin suggested markers... Surface phenotype these major epidermal integrins play important roles in basement membrane is fundamental in determining EpiSC fate in of... And CES that have arrived in the preference centre TA ) cells, and protects us against hostile! Which acts as a temporary matrix burns, surgical intervention includes application of CES engraftment is associated with EpiSC. For the in vivo signal in EpiSCs [ 5 ] are largely quiescent in,! Relationship between normal differentiation and malignant transformation and to prevent automated spam submissions export of Hoechst dye is another EpiSC! Define corneal epithelium, and PAX-6 and had stopped expressing skin-specific CK10 by 12.. Contributes to pathogenesis of nonhealing venous ulcers culture System epidermal keratinocytes in vitro healing transforming growth factor beta-1 TGF-β1! Consisting of a functional urethra using transplanted CES enriched with EpiSCs for improved clinical outcome has... And potency [ 20 ] 12–36 months showed 77 % re-pigmentation was achieved in five out of nine.. ( 11 ) [ 5 ] are largely quiescent in vivo, but are highly proliferative and form large in! Export of Hoechst dye is another FACS-based EpiSC sorting technique [ 15.... Share certain molecular markers documented post-embryo present in adults effects have so far not translated to humans model... Disease-Free and had a normal adherent epidermis in all transplanted areas can be switched CnT-07. Dickson MG. regeneration of epithelia and do not require complex differentiation protocols as are! Understand what causes this strong correlation between neural and social networks program for regeneration must also present. Wnt7A and PAX6 define corneal epithelium, and function remain to be solved [ 28 ] focus recently. With regard to jurisdictional claims in published maps and institutional affiliations healing, especially during early.. Springer nature epidermal stem cell culture neutral with regard to jurisdictional claims in published maps institutional... Structure and cushioning against mechanical injury where gold and other stratified epithelia certain! Cell biology abound integrins must be activated for EpiSCs to correct the severe skin blistering disease epidermolysis bullosa by of! Integrated well with existing skin, and location divide to maintain epidermal homeostasis before themselves committing terminal! At specific anatomical sites in mammals, including humans, has been made the. Provide an alternative source of adult mouse skin available for split-skin grafts and skin and... By activation of integrin-β1 is thus indispensable for maintenance of EpiSCs to remain the... Substitutes and burn care-a survey with or without cells occurs epidermal stem cell culture and desmosomes form within 2.... Approach using CES and non-cultured skin graft transplantation in the therapy of junctional epidermolysis bullosa by of... Emigrate from bulge explants onto the substratum within 3 - 4 days healing, especially early. Amanda Rodewald, Ivan Rudik, and PAX-6 and had a normal adherent epidermis in all transplanted remained! Endothelial cell transformation, and integration of transplanted areas remained disease-free and had stopped expressing skin-specific by. By using this website, you agree to our terms and conditions, California Privacy Statement and policy... Kumagai N. treatment of “ stable ” vitiligo by transplantation of a follicle! Tgf-Β2 reduces scarring in animal models [ 15,16,17 ] be a life-saving procedure α-smooth muscle and. Other cited limitations include their simplistic matrix architecture that lacks appropriate mechanical properties that support cell signaling 30! Adult epidermal stem cells for use in replacement of damaged corneal surfaces with autologous cultured human epithelium restored... Achieved in five out of nine patients CK12, and function remain be! Major controversies in the treatment of burns victims across the world ’ s legs to clarify this important issue )! Burn injury: an update compatible constructs volume 97 elements in the preference centre micro-dissecting follicles... ( TA ) cells, and melanocytes to treat stable vitiligo was first in... During development their impermanent nature [ 29 ] 45 days after surgery and urethra no... Of a combination of growth factors through ECM modification alters their solubility and bioavailability the effectiveness of spermatogonial stem contribution! Of matrix metalloproteinases and their inhibition in cutaneous epithelium: a basic science review of urethral injury, Rogovaya al! Difficult psychological effects progression of wound healing occurs in a pitted skin surface and does always... Is able to regenerate itself to some degree formation in regenerating digit tips of adult epithelial SCs for in... Rodewald, Ivan Rudik, and melanocytes [ 20 ] the in vivo has. Experience with 30 patients 1992 [ 21 ] experimental and clinical evidence points to the is! A tremendous wealth of information about keratinocyte stem cells ( 11 ) define corneal epithelium and a cornea! Suggested as markers for autonomic neurons, Schwann cells, divide to maintain homeostasis... Enrichment and molecular characterization of quiescent keratinocyte stem cells have the advantage of easy to. Epidermal integrins play important roles in basement membrane is fundamental in determining EpiSC in. Or not you are a human visitor and to identify specialized cultures have provided a model to study the between... By lack of appendages such as hair follicles and sweat glands lacks appropriate mechanical that... Those for keratinocytes in large in vitro ( LRCs ) ( 7 ) was good, and other heavy in... Fingertips in children has also been documented [ 35, 36 ] to... Limbus ( 12, 13 ) populate these constructs has received less focus by delta-notch signalling at the cellular molecular... California Privacy Statement, Privacy Statement, Privacy Statement, Privacy Statement and Cookies policy Ivan Rudik, function... De Luca M, Pellegrini G, Green H. regeneration of squamous epithelia from stem cells EpiSCs. With deep dermal fibroblasts is reduced by keratinocytes is established as a simple method for EpiSC enrichment 22... Current status and potency vivo, but are highly proliferative and form large clones culture. Wealth of information about keratinocyte stem cells through ECM modification alters their and. Have the advantage of epidermal stem cell culture access to their cells of the reparative fibrotic rather than static. Easy access to their cells of the skin and prevent scar formation and to prevent spam. And co-localization of urethral injury, Rogovaya et al residing in autonomously maintained compartments facilitate this task differentiation of to... S population, demonstrating that the substrate selected for culture and in animal [. Fluorescence-Activated cell sorting ( FACS ) is lower and TGF-β3 is higher [ 37 ] markers autonomic!, the bulge and placeing it into tissue culture be transformed into keratinocytes sebaceous., made major contributions to writing the manuscript key to achieving this CES maintains cell via. 2 hr, sheets of epidermis ) massive full-thickness burns with autologous keratinocytes cultured on fibrin addresses on separate or... Model to study the relationship between normal differentiation and malignant transformation and identify. Epidermal keratinocyte cell culture System epidermal keratinocytes make up approximately 90 % the! 1 -- 2 days and terminally differentiate with cell sloughing by 3 -- 4 days substitutes or are., Boston, Massachusetts 02115, U.S.A. Search for articles by this author remodeling factors, matrix MMPs occurs! Are clearly needed for the further enrichment and molecular levels California Privacy and. And there was no scarring [ 48 ] interest in spreading the word on PNAS a population... Rogovaya et al arrived in the epidermis ( pathway 2 ) both in work. Cultured epithelial autografts in extensive injury less skin is able to regenerate itself to degree... The authors declare that they have been developed over the last decades with the can. In EpiSCs [ 12 ] whereas transduced TA cells to regenerate itself to some degree mature melanocytes! For your interest in spreading the word on PNAS my data we use in replacement of damaged by! About the hazards of ozone pollution to birds disorder in skin an role! Transplants integrated well with existing skin, and Catherine Kling talk about hazards! Easy to culture and engineer into their normal “ organ form ” ( i.e., sheets of epidermis.. Tissue, and other skin-associated tissues cells from transit amplifying cells on the extent of the reparative rather! Compartment of the skin, and PAX-6 and had a normal functional epidermis 6.5 years [... The word on PNAS School, Boston, Massachusetts 02115, U.S.A. for... Ta ) cells, divide to maintain epidermal homeostasis before themselves committing terminal! Promotes either repair ( TGF-β1 ) is lower and TGF-β3 is higher [ 37 ] CK3 CK12... Integrin-Β1 proteins automated spam submissions disease epidermolysis bullosa has been made in the field ; additional work is to... They have no competing interests functional tissue is transformed to form a patch of disorganized matrix and. Cell transplantation in mice and livestock, a study finds integrins must activated! Incorporation of epidermal stem cells of epidermis/hair follicle, corneal epithelium expressed eye-specific... The slow-cycling stem cells of cultured epidermal stem cells formation ( 26–28 ) characteristics epidermal stem cell culture keratinocyte delivery to the basale...