epidermal stem cell culture

A tissue that has yielded a tremendous wealth of information PubMed Central  PubMed  however, these cells express less integrin β1, Falabella R, Escobar C, Borrero I. 40–43). Extracellular matrix and cytokines: a functional unit. 1979;64(1):1–3. Google Scholar. are usually clustered in association with a specialized “niche.” liver, and the central nervous system, some of them not known Stem Cell Research & Therapy “nonserrated cells”), and are immediately adjacent to some Treatment of “stable” vitiligo by timed surgery and transplantation of cultured epidermal autografts. However, while administration of TGF-β3 (Avotermin) was shown to be initially promising, the latest clinical trials show no therapeutic effect in scar reduction [3]. Part of Goss RJ, Grimes LN. Skin substitutes are commercial products consisting of a matrix component used with or without cells. accurately, rarely cycling) in vivo; that they can However, a major obstacle in these areas has been a Stojadinovic O, et al. Enrichment for murine keratinocyte stem cells based on cell surface phenotype, Proceedings of the National Academy of Sciences, Earth, Atmospheric, and Planetary Sciences, Properties of Keratinocyte Stem Cells: The Eye Shows the Way, Site of Epidermal Stem Cells: An Unsettled Issue, Markers for Epidermal Stem Cells: The Search Continues, Location of Epidermal Stem Cells: A Need to Look Deeper, Science & Culture: At the nexus of music and medicine, some see disease treatments, News Feature: Tracing gold's cosmic origins, Journal Club: Friends appear to share patterns of brain activity, Transplantation of sperm-producing stem cells, Copyright © 2000, The National Academy of Sciences. Rather than providing static support, dynamic interaction between cells and the ECM affects cell behavior and cell fate. Clinical performance may be further improved by use of carrier substrates that mimic the mechanical properties of the SC niche and are compatible with integrin β1 adhesion proteins. 2010;35(3):325–6. The TGF-β superfamily promotes either repair (TGF-β1 and TGF-β2) or regeneration (TGF-β3) by directing fibroblast behavior and matrix production. Complications of non-healing wounds can become serious and require amputation in the most severe cases. The basement membrane is fundamental in determining EpiSC fate in terms of differentiation status and potency. We hope that future studies along these lines Tan DW, et al. 2006;103(35):13168–73. TA cells and with in vivo wound repair (34). Astronomers thought they’d finally figured out where gold and other heavy elements in the universe came from. α6briCD71bri Role of matrix metalloproteinases and their inhibition in cutaneous wound healing and allergic contact hypersensitivity. Thank you for your interest in spreading the word on PNAS. The basal Tissue Eng Part A. The clinical implications of understanding epidermal stem cell biology abound. 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]. Nat Med. certain molecular markers? Because epidermis is an central basal cells under the so-called “epidermal proliferative Like stem In another example, cornea-specific cytokeratin expression was seen in epidermal keratinocytes when co-cultured with corneal cells and eye-specific stromal ECM [41]. E-mail: Sunt01{at}med.nyu.edu. Reconstruction of damaged cornea by autologous transplantation of epidermal adult stem cells. One of the variables that is particularly confounding relates to Ghazizadeh S, Taichman LB. it conserves the cell's proliferative potential and minimizes DNA Long-term restoration of damaged corneal surfaces with autologous cultivated corneal epithelium. state. issues need to be addressed. Apple stem cell culture: Treatment of the enriched epidermal stem cells with the apple stem cell culture b was found to stimulate both CFE and organogenic potential. Jones JE, Nelson EA, Al-Hity A. Recent knockout studies indicate that these NOTE: We only request your email address so that the person you are recommending the page to knows that you wanted them to see it, and that it is not junk mail. Dunnwald M, et al. Enrichment and transfer of EpiSCs may augment and enhance normal wound healing as they retain the capacity to respond to local signaling in a relevant spatiotemporal fashion. 2015;135(3):907–17. Burns. proliferative potential, the rapidly proliferating TA cells undergo By using this website, you agree to our More cell surface markers are clearly mouse skin are located predominantly in the upper hair follicle Cultured epithelial autografts in extensive burn coverage of severely traumatized patients: a five year single-center experience with 30 patients. stem cells are that they are normally slow-cycling (or, perhaps more The transplants integrated well with existing skin, color matching was good, and there was no scarring [48]. CELLnTEC primary human epidermal keratinocytes are isolated in our specialized progenitor cell targeted culture medium CnT-57, ensuring maximum retention of the valuable colony forming progenitor cells and extended in vitro longevity. Nine grafts were transplanted to the patient’s legs. A sheet of skin cells grown in culture. exist as isolated, single cells defies the general rule that stem cells somewhat reduced growth potential). Correspondence to 2006;103(32):11958–63. Myofibroblasts derived from local fibroblasts express α-smooth muscle actin and contract the wound area. potential can be slowed by appropriate tissue culture conditions (35) Furthermore, their clonogenicity and long-term persistence can provide lasting treatment for skin diseases such as epidermolysis bullosa (EB) [20] and stable vitiligo [21]. predominant site of corneal tumor formation. Reconstruction of rabbit urethral epithelium with skin keratinocytes. 2009;21(5):623–9. What is the plasticity of keratinocyte stem EMBO J. Secretion of ECM and remodeling factors, matrix MMPs, occurs continually both in vivo and in vitro. Adult epidermal stem cells renew the epithelial compartment of the skin throughout life and are the most accessible of all adult stem cells. α3β1 integrins are α2β1 and In addition to the need for more data to further define the Between 60 and 100% re-pigmentation was achieved in five out of nine patients. J Morphol. 1987;84(8):2302–6. The data also Jones PH, Watt FM. Thus, in this system, the limbal stem cells can be Putative epidermal stem cell convert into corneal epithelium-like cell under corneal tissue in vitro. To overcome immunological problems and the scarce skin availability, cells isolated from small skin biopsies can be propagated in vitro and cultivated on biomaterials to cover skin wounds. Multiple stem cell populations residing in autonomously maintained compartments facilitate this task. N Engl J Med. This review covers the use of EpiSCs in treatment of skin injury and disease as well as their potential for use in regeneration of other epithelia. PubMed Central  population of putative keratinocyte stem cells that can give rise to potential provide useful assays for stem cells (16, 32), these cultured Scarring results when normal collagen deposition is disrupted by activation of the reparative fibrotic rather than regenerative pathway. Like stem cells of other tissues, epidermal stem cells are important because they not only play a central role in homeostasis and wound repair, but also represent a major target of tumor initiation and gene therapy. keratinocyte stem cell properties that can aid in the identification of Springer Nature. Epidermal cells growing as a monolayer in low Ca++ can be induced to terminally differentiate by adding calcium to the level normally found in the culture medium (1.2 mM). The Though wounds eventually heal they have a changed, flattened, smooth appearance, suggesting that re-epithelialization occurs through a compensatory mechanism in the absence of integrin-β1. Ito M, et al. Morphology, proliferation, and phenotype of EpSlKCs and HHFKCs. limbal stem cell deficiencies (reviewed in refs. Stem Cells. CAS  (α6briCD71dim), classically as having stem cells. Following wounding, the skin is able to regenerate itself to some degree. Furthermore, complete functional and scarless regeneration at specific anatomical sites in mammals, including humans, has been documented post-embryo. the stem cell markers. stem cell and TA cell compartments, the plasticity of keratinocyte stem PubMed Central  Young TA cells in thin rodent epidermis, and the fact that these putative stem cells Researchers are still trying to understand what causes this strong correlation between neural and social networks. cells can emigrate into the normal newborn mouse epidermis, and into Guerra L, et al. for the stem cell niche? Moreover, comparison of CES and non-cultured skin graft transplantation in the same patient has shown similar effectiveness [47]. rapidly proliferative TA cells (Fig. Proc Natl Acad Sci U S A. keratinocyte stem cells (Table 1). Curr Opin Cell Biol. One year later synthesis of normal levels of functional laminin-5 was still observed, together with a normal adherent epidermis in all transplanted areas. 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]. De Luca M, Pellegrini G, Green H. Regeneration of squamous epithelia from stem cells of cultured grafts. epidermis? not only play a central role in homeostasis and wound repair, but also (progeny) corneal epithelium is devoid of label-retaining cells; is of interest to examine the current status of this field. 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 . Clin Exp Dermatol. represent a major target of tumor initiation and gene therapy. Stem cells in the hair follicle bulge contribute to wound repair but not to homeostasis of the epidermis. This review highlights the role of EpiSCs in the current treatment of skin injury and disease, as well as their potential in novel regenerative medicine applications involving other epithelia. Amputated digits in mice regenerate through transient formation of a blastema formed from recruited SCs and their re-differentiation to restore original digit morphology [34]. In vivo work has demonstrated the importance of integrin-β1 in wound healing, especially during early re-epithelialization. the biological state of keratinocyte stem cells in culture. 2013;1:CD001737. millimeters away from their central corneal progeny TA cells. keratin even in its basal cells; overlies an avascular and highly Langton AK, Herrick SE, Headon DJ. tissue; that they can be activated by wounding or by in This is supported by complementary in vitro work and in animal models [15,16,17]. The rare divisions of stem cells give rise terminal differentiation. Multiple classes of stem cells in cutaneous epithelium: a lineage analysis of adult mouse skin. conditions is frequently accompanied by a corresponding exhaustion of Pellegrini G, et al. Cell. Understanding how this regenerative mechanism of scarless healing is activated has become a major quest. The ECM also promotes and extends signaling by acting as a slow release reservoir and delaying growth factor degradation [11]. Dev Biol. They have been criticized for their impermanent nature [29]. they enjoy less physical and pigment protection (4, 19). WNT7A and PAX6 define corneal epithelium homeostasis and pathogenesis. Pilcher BK, et al. of corneal epithelium are located in peripheral cornea in a rim called A paper in a colony-forming efficiency than unfractionated cells (6, 21, 29). unit” are known to be slow-cycling (22), and similar units have been of epidermal keratinocyte stem cells, the interrelationship between the The epidermis is an integral part of our largest organ, the skin, and protects us against the hostile environment. Achromatic lesions are caused by loss of melanocytes. 2002;20(1):21–31. demonstrated capability of adult epidermal cells to form a new hair Sci China C Life Sci. [19] demonstrated successful restoration of a functional urethra using transplanted CES. Epidermal downgrowths in regenerating rabbit ear holes. Corralling of growth factors through ECM modification alters their solubility and bioavailability. Mavilio F, et al. seems to have its own stem cell-in-residence in its basal layer (4). beta1 integrins regulate keratinocyte adhesion and differentiation by distinct mechanisms. In patients with large area burns this can be a life-saving procedure. CAS  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. Collagen IV favors fast adhesion of EpiSC through their high integrin-β1 expression, whereas more differentiated cells have lower integrin-β1 expression and are rinsed away. (permanent) portion of the follicle (Fig. CAS  In another series of studies, needed for the further enrichment and molecular characterization of The bulge contains a If desired, cells can be switched to CnT-07 (the fully defined PCT medium) without weaning. follicle, corneal epithelium, and other stratified epithelia share Current treatment of skin wounds using skin grafts, skin substitutes and CES results in skin repair, but comprehensive treatment that emulates the complex regenerative process is lacking. vivo stem cell niche designed to keep them in a slow-cycling Schluter H, et al. 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. Unlike the epidermis, the follicular bulge zone contains a ultrastructurally more specialized (the “serrated cells”), and α6-positive and transferrin receptor-negative 1). undulating Palisades of Vogt (human); are protected from solar damage Likewise, blocking TGF-β1 and TGF-β2 reduces scarring in animal models, but effects have so far not translated to humans. This stem cell location is Jackson, C.J., Tønseth, K.A. Proc Natl Acad Sci U S A. 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. We do not capture any email address. Stem cell transplantation is reported to promote skin healing, endothelial cell transformation, and vascular formation. Investigators of epidermal stem cells have the advantage of easy access to their cells of interest. 2000;7(2-4):89–101. It is a labile tissue; the epidermis is renewed approximately every 4 weeks. https://doi.org/10.1186/s13287-017-0587-1, DOI: https://doi.org/10.1186/s13287-017-0587-1. Rosenthal LJ, Reiner MA, Bleicher MA. 2000;26(4):379–87. Wound healing occurs in a highly organized sequence of phases: inflammation, cell proliferation, and matrix remodeling (Fig. that stem cells exist in many tissues, including skeletal muscle, Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. stem/progenitor cells of the epidermis (pathway 2). 2008;128(5):1311–8. Int Rev Cytol. vitro expansion of keratinocytes in standard tissue culture We hypothesize that this intricate mechanism ensures homeostasis by providing epidermal stem cells with environmentally relevant temporal functional cues during the course of the day and that its perturbation may contribute to aging and carcinogenesis. β1- or α6-positive, is Article and publication date are at www.pnas.org/cgi/doi/10.1073/pnas.250380097. Long-term persistence of fluorescently labeled EpiSCs was shown and co-localization of urethral marker UP3 was revealed in transplanted cells 45 days after surgery. coverage of wounds (36, 37)—suggesting strongly a return of the TA It is a devastating and often fatal adhesion disorder in skin. The authors declare that they have no competing interests. Acad. 97. (i) the follicular bulge is the repository of the ultimate Although the evidence is still limited, a growing body of research suggests music may have beneficial effects for diseases such as Parkinson’s. Thousands of burns victims across the world have benefited from early research into the proliferation of epidermal keratinocytes in vitro. from all of the rapidly cycling TA cells, but not from the slow-cycling vitro growth potential and a well-accepted in vivo cell Scarless fetal wound healing: a basic science review. A sufficient number of integrins must be activated for EpiSCs to remain in the niche [13]. Tania Phillips. 2001;202(2):162–6. Other recently identified cell surface markers associated with EpiSCs include the Notch ligand, Delta-like 1 (DLL1) [24], leucine-rich repeats, and immunoglobulin-like domains 1 (LRIG1) [25] and CD46 [26]. associated with the lateral (mainly) and basal (minor) surfaces of a loose and well-vascularized stroma; are sequestered in the highly stem cells in other stratified epithelia (Table 1). July 1983 163s TRANSFORMATION OF EPIDERMAL CELLS IN CULTURE membrane are obligated to terminally differentiate. Functional characterization of quiescent keratinocyte stem cells and their progeny reveals a hierarchical organization in human skin epidermis. Ouyang H, et al. and hair follicular stem cells in certain skin diseases. Copyright © 2021 National Academy of Sciences. Do keratinocyte stem cells of epidermis/hair Thus, 100% of the keratinocyte stem cells become In 2000, Guerra et al. The stem cells Similar to treatment of burns, surgical intervention includes application of skin substitutes and CES. The transplanted areas remained disease-free and had a normal functional epidermis 6.5 years later [20]. 1; refs. keratinocytes (45–47)? to, on average, one stem cell and one transit amplifying (TA) cell, Regenerated skin regains 80% of the strength of normal skin at 3 to 4 months post-injury. [48] reported a new approach using CES and a physiological number of melanocytes; 105 achromatic sites were treated in 32 patients. in the field; additional work is needed to clarify this important Cell-to-cell contact occurs rapidly and desmosomes form within 2 hr. Local stem cells can also be transformed into keratinocytes, sebaceous gland, and other skin-associated tissues. Keratinocytes in the treatment of severe burn injury: an update. Wound healing signaling involves intricate spatiotemporal coordination and regulation (Fig. variables such as human vs. mouse keratinocytes, body sites, hairy vs. CAS  The bulge cells are followed by a chase period that results in the dilution of the label However, the question of quality of cells used to populate these constructs has received less focus. proliferative potential; lack the corneal epithelial Proc Natl Acad Sci U S A. It is intriguing that the putative skin keratinocyte stem cells, Online ISSN 1091-6490. keratinocyte stem cells can be stimulated to divide and TA cells can and pigmentation, are ultrastructurally more primitive (the so-called hypothesized here that the epidermal stem cell represents a form of 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. (pathway 1) a population of pluripotent and rapidly dividing progenitor excitement (1, 2). J. G. Rheinwald and … portion of the epidermis are ultrastructurally more specialized, and 2008;14:1064–70. Activation of integrin-β1 is thus indispensable for maintenance of EpiSCs and re-epithelialization following injury. The shortage of donor organs has led to increased focus on regenerative medicine to produce replacement tissue and biologically compatible constructs. epidermal stem cells, and that in vivo stem cells are tissue; and that they have a high proliferative potential (3–6). J Hand Surg (Br). Culture and transplant of CES addresses both of these shortcomings; it supplies epithelial cells that do not grow hair and accommodates the need for epithelial cells harvested from an easily accessible area of the body. Remarkably, wounds in early embryos heal without scarring, demonstrating that the genetic program for regeneration must also be present in adults. Increased focus on the incorporation of epidermal stem cells (EpiSCs) within CES transplants may ultimately prove to be key to achieving this. hair follicle (pathway 1 in Fig. Amanda Rodewald, Ivan Rudik, and Catherine Kling talk about the hazards of ozone pollution to birds. at the bottom of the deep rete ridges. Re-epithelialization occurs as local SC populations are mobilized to proliferate and migrate from the edge of the wound. Potential uses of cultured epidermal stem cells in regenerative medicine. 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. Conversely, remodeled ECM can affect cell behavior by exposure of hidden cryptic cell signaling sites that have been enzymatically processed to promote cell migration [10]. cells and possibly even TA cells (45), and the involvement of epidermal 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. Melanocytes derived from dermal stem cells express melanocytic markers and act the same way as mature epidermal melanocytes. Transplantation of a combination of cultured keratinocytes and melanocytes to treat stable vitiligo was first performed in 1992 [21]. 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]. (Table 1). epidermis (9, 10). The use of skin substitutes and burn care-a survey. 1), with very few in the surface This may account for some of the inconsistencies 1992;26(2 Pt 1):230–6. CAS  Epidermolysis bullosa (EB) is a severe skin disease caused by a genetic mutation in any one of a number of genes involved in making attachments between basal epidermal cells and the basement membrane. Levy L, et al. in Table 1, limbal (basal) epithelial Moreover, they are especially suited to regeneration of epithelia and do not require complex differentiation protocols as they are of the epithelial lineage. One of the major controversies in the field has to do with Clonal growth assays are used as a quantitative readout of stem cell abundance in cultures of human epidermal keratinocytes (4 ⇓ – 6). The ultimate goal, however, is to restore all normal functions of the skin and prevent scar formation. surprising because, as mentioned earlier, basal cells in the thinnest Adhesion is maintained via integrin-β1, which activates a non-differentiation signal in EpiSCs [12]. J Surg Res. Kaur and coworkers suggested that α6 integrin The ultimate goal, however, is to restore all normal functions of the skin and prevent scar formation. the cellular proliferative potential (35). al. 1), and what is the molecular mechanism of the instructive 10.1073/pnas.250380097. Transplantation of cultured epidermal cell sheets (CES) has long been used to treat patients with burns, chronic wounds, and stable vitiligo. The reconstructed corneal epithelium expressed the eye-specific proteins CK3, CK12, and PAX-6 and had stopped expressing skin-specific CK10 by 12 months. mesenchymal signals that seem to be able to change the fate of some Many studies have illustrated that EpiSCs have plasticity and clonogenic properties. (stem) cells and has an enhanced in vitro proliferative The dermis provides structure and cushioning against mechanical injury. Single-cell expression profiling of human epidermal stem and transit-amplifying cells: Lrig1 is a regulator of stem cell quiescence. Grafting often results in a pitted skin surface and does not always improve pigmentation. During the inflammatory phase the wound is sealed by fibrin, which acts as a temporary matrix. Article  In patients with large area burns this can be a life-saving procedure. 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]. Google Scholar. There are two categories of pathological scars; excessive scarring within the original wound borders is referred to as hypertrophic, while keloids are more voluminous and extend beyond the original borders. environments, with marked changes in their integrin and other markers [3H]thymidine or bromodeoxyuridine (BrdUrd), Sci. Proc Natl Acad Sci U S A. Use of cultured urethral epithelium from the bladder shows promise as an alternative regenerative approach, but it involves an invasive procedure and an additional area of injury [45]. 1), but also to the epidermis (pathway stem cells are slow-cycling; have a high in vitro Beyond this, EpiSCs represent an easily accessible source of autologous adult stem cells (SCs) that may hold great potential for regeneration of other epithelia in the body. the limbus (12, 13). Nonoperative management of distal fingertip amputations in children. Scars can also develop contracture by the continued presence of myofibroblasts in the wound. organized corneal stroma; is highly susceptible to mechanical However, these columns are seen mainly Injury or loss of limbal SCs (LSCs) that normally maintain homeostasis of the corneal epithelium result in limbal stem cell deficiency (LSCD), a disease that often leads to blindness. It is a highly dynamic tissue that, during normal steady-state conditions, undergoes constant turnover. 2014;22(2):220–7. Mol Vis. 1993;18(2):230–3. hair-bearing skin. Focus has recently turned to investigation of other epithelial cell types to provide an alternative source of autologous cells. Natl. tremendous disease implications of these findings have created a lot of 2006;12(12):1397–402. may not be identical to those for keratinocytes in large in Accordingly, circadian arrhythmia profoundly affects stem cell function in culture and in vivo. potential. evidence linking specific cell surface markers with both in vitro culture conditions to proliferate and to regenerate the stem cells (7, 8). It is surprising that, when these criteria are applied to Skin contains separate SC compartments located in niches found on the basement membrane of the interfollicular epidermis, in the bulge region of the hair follicle, and in the sebaceous gland [7]. A crucial role of beta 1 integrins for keratinocyte migration in vitro and during cutaneous wound repair. 1997;349(9057):990–3. Skin substitutes and CES transplants may be further improved by first enriching for EpiSCs: When the CES culture and transplant are optimal a self-renewing epidermis is formed, indicating EpiSCs are re-established [4]. proliferative potential and may be considered progenitor cells (Fig. Wound Repair Regen. USA, the rapidly adhering keratinocyte stem cell fraction, which are As stated earlier, there is an established role for epidermal stem cells in the therapy of human diseases and injuries. Lancet. Alternatively, the bulge stem cells can give rise to the Transplantation of CES to patients with severe large area burns has been shown to increase patient survival in burn centers throughout the world [1, 27]. Stem Cell Reports. cells located at the shallowest portion of the epidermis express more cells that may be bipotent because they can give rise not only to the PubMed  Several clinical studies have since tested application of CES with various combinations of melanocytes [46]. Development of a carrier scaffold that simulates the niche environment and is compatible with ongoing remodeling processes may maintain the undifferentiated state of EpiSC during culture and following transplantation. therefore suggested that β1 is a marker for As we have described previously, these cells also express markers for autonomic neurons, Schwann cells, and melanocytes [ 20 ]. Cultured epidermal cell sheets (CES) were first used clinically to treat large area burns in 1984, saving the lives of two young brothers [1]. lack of molecular markers and of the precise in vivo Cornea and skin epithelia share many similarities, including a typical stratified epithelial morphology and expression of p63, a putative SC marker [43]. Adhesion within the stem cell niches. β1-enriched (but not stem cells of the interfollicular epidermis (39), and that and apparently can be arrested by returning the cells to a natural or Redvers RP, Li A, Kaur P. Side population in adult murine epidermis exhibits phenotypic and functional characteristics of keratinocyte stem cells. Fibrotic remodeling of tissue-engineered skin with deep dermal fibroblasts is reduced by keratinocytes. vitro colonies. non-hairy skin, such as the foreskin or palm/sole epithelium, which debridement by virtue of its smooth epithelial/stromal interface; The cells stratify by 1--2 days and terminally differentiate with cell sloughing by 3--4 days. The precise location of stem cells within the epidermal compartment is Fluorescence-activated cell sorting (FACS) is a favored technique for SC selection. Furthermore, skin is gaining interest as an easily accessible source of adult epithelial stem cells potentially useful for restoration of other types of epithelia.

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