scholarly journals Therapeutic Potential of Stem Cells in Follicle Regeneration

2018 ◽  
Vol 2018 ◽  
pp. 1-16 ◽  
Author(s):  
Agnieszka Owczarczyk-Saczonek ◽  
Magdalena Krajewska-Włodarczyk ◽  
Anna Kruszewska ◽  
Łukasz Banasiak ◽  
Waldemar Placek ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Hair Follicle ◽  
Therapeutic Potential ◽  
Cell Activity ◽  
Hair Follicles ◽  
Treatment Technique ◽  
Androgenic Alopecia ◽  
The Metabolic Syndrome ◽  
Increased Risk

Alopecia is caused by a variety of factors which affect the hair cycle and decrease stem cell activity and hair follicle regeneration capability. This process causes lower self-acceptance, which may result in depression and anxiety. However, an early onset of androgenic alopecia is associated with an increased incidence of the metabolic syndrome and an increased risk of the cardiac ischaemic disease. The ubiquity of alopecia provides an encouragement to seek new, more effective therapies aimed at hair follicle regeneration and neoregeneration. We know that stem cells can be used to regenerate hair in several therapeutic strategies: reversing the pathological mechanisms which contribute to hair loss, regeneration of complete hair follicles from their parts, and neogenesis of hair follicles from a stem cell culture with isolated cells or tissue engineering. Hair transplant has become a conventional treatment technique in androgenic alopecia (micrografts). Although an autologous transplant is regarded as the gold standard, its usability is limited, because of both a limited amount of material and a reduced viability of cells obtained in this way. The new therapeutic options are adipose-derived stem cells and stem cells from Wharton’s jelly. They seem an ideal cell population for use in regenerative medicine because of the absence of immunogenic properties and their ease of obtainment, multipotential character, ease of differentiating into various cell lines, and considerable potential for angiogenesis. In this article, we presented advantages and limitations of using these types of cells in alopecia treatment.

scholarly journals CCN2 modulates hair follicle cycling in mice

2013 ◽  
Vol 24 (24) ◽  
pp. 3939-3944 ◽  
Author(s):  
Shangxi Liu ◽  
Andrew Leask
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Hair Follicle ◽  
Cell Activity ◽  
Adult Life ◽  
Tissue Growth ◽  
Hair Follicles ◽  
Outer Root Sheath ◽  
Root Sheath ◽  
Dermal Papillae

It is critical to understand how stem cell activity is regulated during regeneration. Hair follicles constitute an important model for organ regeneration because, throughout adult life, they undergo cyclical regeneration. Hair follicle stem cells—epithelial cells located in the follicle bulge—are activated by periodic β-catenin activity, which is regulated not only by epithelial-derived Wnt, but also, through as-yet-undefined mechanisms, the surrounding dermal microenvironment. The matricellular protein connective tissue growth factor (CCN2) is secreted into the microenvironment and acts as a multifunctional signaling modifier. In adult skin, CCN2 is largely absent but is unexpectedly restricted to the dermal papillae and outer root sheath. Deletion of CCN2 in dermal papillae and the outer root sheath results in a shortened telogen-phase length and elevated number of hair follicles. Recombinant CCN2 causes decreased β-catenin stability in keratinocytes. In vivo, loss of CCN2 results in elevated numbers of K15-positive epidermal stem cells that possess elevated β-catenin levels and β-catenin–dependent reporter gene expression. These results indicate that CCN2 expression by dermal papillae cells is a physiologically relevant suppressor of hair follicle formation by destabilization of β-catenin and suggest that CCN2 normally acts to maintain stem cell quiescence.

scholarly journals A Mouse Model for Studying Stem Cell Effects on Regeneration of Hair Follicle Outer Root Sheaths

2020 ◽  
Vol 15 (1) ◽  
pp. 41-50
Author(s):  
Jingxu Guo ◽  
Shuwei Li ◽  
Hongyang Wang ◽  
Tinghui Wu ◽  
Zhenhui Wu ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Mouse Model ◽  
Hair Follicle ◽  
Smooth Muscle Actin ◽  
Hair Follicles ◽  
Alpha Smooth Muscle Actin ◽  
Papillary Structure ◽  
Glass Membrane

AbstractObjectiveStem cells hold promise for treating hair loss. Here an in vitro mouse model was developed using outer root sheaths (ORSs) isolated from hair follicles for studying stem cell-mediated dermal papillary regeneration.MethodsUnder sterile conditions, structurally intact ORSs were isolated from hair follicles of 3-day-old Kunming mice and incubated in growth medium. Samples were collected daily for 5 days. Stem cell distribution, proliferation, differentiation, and migration were monitored during regeneration.ResultsCell proliferation began at the glass membrane periphery then spread gradually toward the membrane center, with the presence of CD34 and CD200 positive stem cells involved in repair initiation. Next, CD34 positive stem cells migrated down the glass membrane, where some participated in ORS formation, while other CD34 cells and CD200 positive cells migrated to hair follicle centers. Within the hair follicle matrix, stem cells divided, grew, differentiated and caused outward expansion of the glass membrane to form a dermal papillary structure containing alpha-smooth muscle actin. Neutrophils attracted to the wound site phagocytosed bacterial and cell debris to protect regenerating tissue from infection.ConclusionIsolated hair follicle ORSs can regenerate new dermal papillary structures in vitro. Stem cells and neutrophils play important roles in the regeneration process.

scholarly journals Mechanotransductive Differentiation of Hair Follicle Stem Cells Derived from Aged Eyelid Skin into Corneal Endothelial-Like Cells

2021 ◽  
Author(s):  
Christian Olszewski ◽  
Jessika Maassen ◽  
Rebecca Guenther ◽  
Claudia Skazik-Voogt ◽  
Angela Gutermuth
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Hair Follicle ◽  
Hair Follicles ◽  
Adherent Cell ◽  
Promising Alternative ◽  
Eyelid Skin ◽  
Hair Follicle Stem Cells ◽  
Follicle Stem Cells

AbstractCorneal endothelial insufficiency is one of the leading causes of blindness. The main contemporary treatment for corneal blindness is endothelial keratoplasty, which, however, is unsatisfactory as a medical therapy due to the lack of donor corneas and graft rejection. Therefore, autologous stem cell-based corneal endothelial tissue substitutes may be a promising alternative to conventional grafts in the future. To address the age of most patients suffering from corneal endothelial deficiencies, we investigated the presence and potential of hair-derived stem cells from older tissue donors. Our studies revealed the presence of pluripotency- and neural crest-associated markers in tissue sections from blepharoplasty patients aged 50 to 80 years. In vitro outgrowths from eyelid hair follicles on collagen-coated tissue culture plates revealed a weak decrease in stem-cell potency. In contrast, cells within the spheres that spontaneously formed from the adherent cell layer retained full stem-cell potency and could be differentiated into cells of the ecto- meso and endodermal lineages. Although these highly potent hair follicle derived stem cells (HFSC) were only very slightly expandable, they were able to recognize the biomimicry of the Descemet’s-like topography and differentiate into corneal endothelial-like cells. In conclusion, HFSCs derived from epidermal skin of eyelid biopsies are a promising cell source to provide autologous corneal endothelial replacement for any age group of patients. Graphical Abstract

scholarly journals NANOG Attenuates Hair Follicle-Derived Mesenchymal Stem Cell Senescence by Upregulating PBX1 and Activating AKT Signaling

2019 ◽  
Vol 2019 ◽  
pp. 1-14 ◽  
Author(s):  
Feilin Liu ◽  
Jiahong Shi ◽  
Yingyao Zhang ◽  
Aobo Lian ◽  
Xing Han ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Rna Interference ◽  
Mesenchymal Stem Cell ◽  
Hair Follicle ◽  
Therapeutic Potential ◽  
Akt Signaling ◽  
Akt Inhibitor ◽  
Nanog Expression ◽  
Phosphorylated Akt

Stem cells derived from elderly donors or harvested by repeated subculture exhibit a marked decrease in proliferative capacity and multipotency, which not only compromises their therapeutic potential but also raises safety concerns for regenerative medicine. NANOG—a well-known core transcription factor—plays an important role in maintaining the self-renewal and pluripotency of stem cells. Unfortunately, the mechanism that NANOG delays mesenchymal stem cell (MSC) senescence is not well-known until now. In our study, we showed that both ectopic NANOG expression and PBX1 overexpression (i) significantly upregulated phosphorylated AKT (p-AKT) and PARP1; (ii) promoted cell proliferation, cell cycle progression, and osteogenesis; (iii) reduced the number of senescence-associated-β-galactosidase- (SA-β-gal-) positive cells; and (iv) downregulated the expression of p16, p53, and p21. Western blotting and dual-luciferase activity assays showed that ectopic NANOG expression significantly upregulated PBX1 expression and increased PBX1 promoter activity. In contrast, PBX1 knockdown by RNA interference in hair follicle- (HF-) derived MSCs that were ectopically expressing NANOG resulted in the significant downregulation of p-AKT and the upregulation of p16 and p21. Moreover, blocking AKT with the PI3K/AKT inhibitor LY294002 or knocking down AKT via RNA interference significantly decreased PBX1 expression, while increasing p16 and p21 expression and the number of SA-β-gal-positive cells. In conclusion, our findings show that NANOG delays HF-MSC senescence by upregulating PBX1 and activating AKT signaling and that a feedback loop likely exists between PBX1 and AKT signaling.

scholarly journals Targeted inactivation of integrin-linked kinase in hair follicle stem cells reveals an important modulatory role in skin repair after injury

2011 ◽  
Vol 22 (14) ◽  
pp. 2532-2540 ◽  
Author(s):  
Kerry-Ann Nakrieko ◽  
Alena Rudkouskaya ◽  
Timothy S. Irvine ◽  
Sudhir J. A. D'souza ◽  
Lina Dagnino
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Hair Follicle ◽  
Hair Follicles ◽  
Stem Cell Population ◽  
Epidermal Surface ◽  
Hair Follicle Stem Cells ◽  
Integrin Linked Kinase ◽  
Hair Follicle Growth ◽  
Follicle Stem Cells

Integrin-linked kinase (ILK) is key for normal epidermal morphogenesis, but little is known about its role in hair follicle stem cells and epidermal regeneration. Hair follicle stem cells are important contributors to newly formed epidermis following injury. We inactivated the Ilk gene in the keratin 15–expressing stem cell population of the mouse hair follicle bulge. Loss of ILK expression in these cells resulted in impaired cutaneous wound healing, with substantially decreased wound closure rates. ILK-deficient stem cells produced very few descendants that moved toward the epidermal surface and into the advancing epithelium that covers the wound. Furthermore, those few mutant cells that homed in the regenerated epidermis exhibited a reduced residence time. Paradoxically, ILK-deficient bulge stem cells responded to anagen growth signals and contributed to newly regenerated hair follicles during this phase of hair follicle growth. Thus ILK plays an important modulatory role in the normal contribution of hair follicle stem cell progeny to the regenerating epidermis following injury.

Donor Hematopoietic Stem Cells Did No Major Contribution to Hair Follicle Repair Either in Short or in Long Term Allogeneic Hematopoietic Stem Cell Transplants Recipients.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 4167-4167
Author(s):  
Alicia Rovo ◽  
Sandrine Meyer-Monard ◽  
Dominik Heim ◽  
Caroline Arber ◽  
Jakob R. Passweg ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Hair Follicle ◽  
Hair Follicles ◽  
Short Term ◽  
Blood Contamination ◽  
Hematopoietic Stem ◽  
Donor Type

Abstract Several reports suggest that hematopoietic stem cell (HSC) develops unexpected plasticity and can form non-hematopoietic tissue. However the intrinsic plasticity of these cells has been questioned suggesting that such cells might fuse with other cells giving the appearance of differentiation. Most of the controversy over the mechanism arises from the techniques that are used to track and characterize the progenitor cell in different tissues. In the clinical setting there are no prospective quantitative studies in the human being. Objective: we assessed in a prospective study the incidence and extent of donor type chimerism in blood and non-hematopoietic cells tissue in allogeneic HSC transplants irrespective of donor type, stem cell source, conditioning and disease category. We focused on tissues with high need of organ repair: following conditioning and free of blood contamination: hair follicles. In a preliminary report we showed hair chimerism results from 53 long term survivors of allogeneic HSCT. In those recipients donor cells did not contribute to hair follicle repair. We now extend the study by increasing the number of long term patients and including short term survivors after successful engraftment. Methods: all consecutive male and female patients above 18 years old, with a full donor chimerism of hemopoiesis at last control were included. The visit included: anamnesis, clinical examination and chimerism from peripheral blood and hair follicles. Chimerism was analyzed by PCR-based amplification of 9 different short tandem repeat (STR) loci and the amelogenin locus, detecting a minor cell population ≥3%. We minimized the risk of blood contamination by careful hair follicles washing according to the procedure used in forensic medicine. The protocol was approved by the Ethics Committee. Results: between April 2003 and July 2004, 145 patients were invited to participate in this study, 119 patients (82%) accepted, 4 patients were excluded due to insufficient hair DNA; therefore the study included 100 long term (≥ 24 months of follow-up) and 15 short term (1–12 month follow-up) patients. Population demographic characteristics and results Conclusions: we observed a high grade of acceptance for participation in the study. In this population all hair follicles chimerism showed 100% recipient alleles, there was no difference between recipients with short or long term follow-up after HSCT. Hematopoietic stem cells from donor did not make a major contribution to repair hair growth in recipients. Contamination by hematopoietic cells can be excluded in this study due to the fact that we found no donor alleles in the hair analyzed. Follow up after HSCT(months) ≥ 24 1–12 N 100 15 Gender Male/Female 59/41 10/ 5 Median age at HSCT 36 (range 6–63) 40 (range 17–50) Median age at follow up 43 (range 20–66) 40 (range 18–51) Median follow up (months) 96 (range 24–264) 8 (range 2–12) Donor gender Male/Female 58/42 9/6 Diagnosis to transplantation Severe aplastic anemia 6 0 Hematological malignancy 94 15 HLA Type donor identical sibling 85 12 matched related 1 0 mismatched related 3 1 matched unrelated 11 2 Source PB/BM 33/67 15/0 Conditioning High intensity 85 13 Low intensity 15 2 Acute GVHD no/yes 25/75 5/10 Chronic GVHD no/yes 41/59 6/9 Blood chimerism 100% donor alleles 98 15 90–95% donor alleles 2 0 Hair chimerism 100% recipient alleles 100 15

scholarly journals 174 ISOLATION, CULTURE AND POTENTIAL USE OF THE PORCINE NEURAL AND EPIDERMAL STEM CELLS

2005 ◽  
Vol 17 (2) ◽  
pp. 238
Author(s):  
J. Motlik ◽  
P. Vodicka ◽  
J. Klima ◽  
K. Smetana ◽  
F. Liu ◽  
...  
Keyword(s):  
Stem Cells ◽  
Hair Follicle ◽  
Therapeutic Potential ◽  
Hair Follicles ◽  
Mammalian Brain ◽  
Epidermal Stem Cells ◽  
Feeder Cells ◽  
Ki 67 ◽  
Potential Marker

The mammalian brain and epidermis contain stem cells, so-called neural stem cells (NSC) and epidermal stem cells (EpSC). To achieve the full therapeutic potential of stem cells, appropriate animal models have to be used to establish the sequence of pathological changes and to test potential therapies to block these changes. In the following studies miniature pigs were used as a biomedical model. We isolated multipotent cells from brains of porcine fetuses for future use in allotransplantation experiments in the inbred miniature pig strain. Brain tissue from 40- and 80-day-old porcine fetuses was mechanically dissociated, and cells were cultured in serum-free F12/DMEM medium with B27 and N2 supplements, EGF and bFGF. In 3–5 days some cells divided and formed floating spheres that were dissociated to single cell suspension and formed secondary spheres in culture. At all time points tested, the spheres represented mixtures of undifferentiated cells stained with nestin and Ki-67 antibodies and already differentiated neurons (Tu-20, MAP2) and glia (GFAP). After being plated on laminin/fibronectin coated coverslips and cultured in medium containing 2% FBS or 1 μM retinoic acid, the spheres adhered to the surface, and flattened, and cells started to migrate out. After immunofluorescence staining with antibodies to neuronal markers Tu-20 and MAP2, glial marker GFAP and oligodendrocyte marker CNPase showed that all the three cell types were present among differentiated cells. The EpSC are characterized by a slow and unlimited proliferation rate and, therefore, they retain labelled precursors of DNA more extensively than other keratinocytes. The main pool of EpSC is located in the bulge region of the hair follicle root sheath. A new procedure to isolate porcine hair follicles including their root sheaths was developed. The keratinocytes that migrated from hair follicles in the presence of feeder cells were poorly differentiated and specifically expressed galectin-1 or galectin-1-binding sites in their nuclei in co-localization with ΔNp63α. The exclusion of feeder cells from experimental system induced formation of spheroid bodies from these keratinocytes. Approximately one-third of these spheroids were able to adhere to a surface precolonized with feeder cells and to start forming normally growing colonies. Porcine hair follicles represent an excellent model for study of the functional phenotype of hair follicle-originated keratinocytes, and the endogenous lectin Gal-1 seems to be a potential marker of the porcine stem cell compartment of the hair follicle under in vitro conditions.

scholarly journals Increased Expression of Zyxin and Its Potential Function in Androgenetic Alopecia

2021 ◽  
Vol 8 ◽  
Author(s):  
Qingmei Liu ◽  
Xiangguang Shi ◽  
Yue Zhang ◽  
Yan Huang ◽  
Kai Yang ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hair Follicle ◽  
Hair Growth ◽  
Ex Vivo ◽  
Cell Activity ◽  
Hair Follicles ◽  
Androgenetic Alopecia ◽  
Pcr Analysis

Androgenetic alopecia (AGA) is the most common progressive form of hair loss, occurring in more than half of men aged > 50 years. Hair follicle (HF) miniaturization is a feature of AGA, and dermal papillae (DP) play key roles in hair growth and regeneration by regulating follicular cell activity. Previous studies have revealed that adhesion signals are important factors in AGA development. Zyxin (ZYX) is an actin-interacting protein that is essential for cell adhesion and migration. The aim of this research was to investigate the expression and potential role of ZYX in AGA. Real-time polymerase chain reaction (RT-PCR) analysis revealed that ZYX expression was elevated in the affected frontal HF of individuals with AGA compared to unaffected occipital HF. Moreover, increased ZYX expression was also observed within DP using immunofluorescence staining. Our in vivo results revealed that ZYX knockout mice showed enhanced hair growth and anagen entry compared to wild-type mice. Reducing ZYX expression in ex vivo cultured HFs by siRNA resulted in the enhanced hair shaft production, delayed hair follicle catagen entry, increased the proliferation of dermal papilla cells (DPCs), and upregulated expression of stem cell-related proteins. These results were further validated in cultured DPCs in vitro. To further reveal the mechanism by which ZYX contributes to AGA, RNA-seq analysis was conducted to identify gene signatures upon ZYX siRNA treatment in cultured hair follicles. Multiple pathways, including focal adhesion and HIF-1 signaling pathways, were found to be involved. Collectively, we discovered the elevated expression of ZYX in the affected frontal hair follicles of AGA patients and revealed the effects of ZYX downregulation on in vivo mice, ex vivo hair follicles, and in vitro DPC. These findings suggest that ZYX plays important roles in the pathogenesis of AGA and stem cell properties of DPC and may potentially be used as a therapeutic target in AGA.

scholarly journals An Intrinsic Oscillation of Gene Networks Inside Hair Follicle Stem Cells: An Additional Layer That Can Modulate Hair Stem Cell Activities

2020 ◽  
Vol 8 ◽  
Author(s):  
Patrycja Daszczuk ◽  
Paula Mazurek ◽  
Tomasz D. Pieczonka ◽  
Alicja Olczak ◽  
Łukasz M. Boryń ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Hair Follicle ◽  
Gene Networks ◽  
Molecular Mechanisms ◽  
Hair Follicles ◽  
Hair Follicle Stem Cells ◽  
Intrinsic Oscillation ◽  
Follicle Stem Cells ◽  
Niche Components

This article explores and summarizes recent progress in and the characterization of main players in the regulation and cyclic regeneration of hair follicles. The review discusses current views and discoveries on the molecular mechanisms that allow hair follicle stem cells (hfSCs) to synergistically integrate homeostasis during quiescence and activation. Discussion elaborates on a model that shows how different populations of skin stem cells coalesce intrinsic and extrinsic mechanisms, resulting in the maintenance of stemness and hair regenerative potential during an organism’s lifespan. Primarily, we focus on the question of how the intrinsic oscillation of gene networks in hfSCs sense and respond to the surrounding niche environment. The review also investigates the existence of a cell-autonomous mechanism and the reciprocal interactions between molecular signaling axes in hfSCs and niche components, which demonstrates its critical driving force in either the activation of whole mini-organ regeneration or quiescent homeostasis maintenance. These exciting novel discoveries in skin stem cells and the surrounding niche components propose a model of the intrinsic stem cell oscillator which is potentially instructive for translational regenerative medicine. Further studies, deciphering of the distribution of molecular signals coupled with the nature of their oscillation within the stem cells and niche environments, may impact the speed and efficiency of various approaches that could stimulate the development of self-renewal and cell-based therapies for hair follicle stem cell regeneration.

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