scholarly journals Nanoscale microenvironment engineering for expanding human hair follicle stem cell and revealing their plasticity

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Peng Chen ◽  
Feifei Zhang ◽  
Zhexiang Fan ◽  
Tianding Shen ◽  
Bingcheng Liu ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hair Follicle ◽  
Tissue Regeneration ◽  
Hair Follicles ◽  
Bmp Signaling ◽  
Signal Molecules ◽  
Layer By Layer ◽  
Cell Homeostasis ◽  
Excellent Research ◽  
Essential Components

Abstract Background Periodically regenerated hair follicles provide an excellent research model for studying tissue regeneration and stem cell homeostasis. Periodic activation and differentiation of hair follicle stem cells (HFSCs) fuel cyclical bouts of hair regeneration. HFSCs represent an excellent paradigm for studying tissue regeneration and somatic stem cell homeostasis. However, these crucial studies are hampered by the lack of a culture system able to stably expand human HFSCs and regulate their fate. Results Here, we use layer-by-layer (LbL) self-assembly with gelatin/alginate to construct a nanoscale biomimetic extracellular matrix (ECM) for an HFSC population. The LbL coating provides ECM and mechanical support for individual cells, which helps to maintain the CD200+α6+ HFSC population to a certain extent. Addition of key signal molecules (FGF-7 and VEGF-A) simulates the minimum essential components of the stem cell microenvironment, thereby effectively and stably expanding HFSCs and maintaining the CD200+α6+ HFSC population. Subsequently, BMP2 loaded to the nanocoated layer, as a slow-release signal molecule, activates BMP signaling to regulate HFSCs’ fate in order to obtain a purified CD200+α6+ HFSC population. Conclusion This system can minimize the microenvironment of HFSCs; thus, stably amplifying HFSCs and revealing their plasticity. Our study thus provides a new tool for studies of hair follicle reconstruction and stem cell homeostasis.

scholarly journals Functional Specificity of the Members of the Sos Family of Ras-GEF Activators: Novel Role of Sos2 in Control of Epidermal Stem Cell Homeostasis

Cancers ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 2152
Author(s):  
Fernando C. Baltanás ◽  
Cynthia Mucientes-Valdivieso ◽  
L. Francisco Lorenzo-Martín ◽  
Natalia Fernández-Parejo ◽  
Rósula García-Navas ◽  
...  
Keyword(s):  
Stem Cell ◽  
Layer Structure ◽  
3D Culture ◽  
Hair Follicles ◽  
Specific Cell ◽  
Epidermal Stem Cell ◽  
Primary Keratinocytes ◽  
Cell Homeostasis ◽  
Primary Mouse

Prior reports showed the critical requirement of Sos1 for epithelial carcinogenesis, but the specific functionalities of the homologous Sos1 and Sos2 GEFs in skin homeostasis and tumorigenesis remain unclear. Here, we characterize specific mechanistic roles played by Sos1 or Sos2 in primary mouse keratinocytes (a prevalent skin cell lineage) under different experimental conditions. Functional analyses of actively growing primary keratinocytes of relevant genotypes—WT, Sos1-KO, Sos2-KO, and Sos1/2-DKO—revealed a prevalent role of Sos1 regarding transcriptional regulation and control of RAS activation and mechanistic overlapping of Sos1 and Sos2 regarding cell proliferation and survival, with dominant contribution of Sos1 to the RAS-ERK axis and Sos2 to the RAS-PI3K/AKT axis. Sos1/2-DKO keratinocytes could not grow under 3D culture conditions, but single Sos1-KO and Sos2-KO keratinocytes were able to form pseudoepidermis structures that showed disorganized layer structure, reduced proliferation, and increased apoptosis in comparison with WT 3D cultures. Remarkably, analysis of the skin of both newborn and adult Sos2-KO mice uncovered a significant reduction of the population of stem cells located in hair follicles. These data confirm that Sos1 and Sos2 play specific, cell-autonomous functions in primary keratinocytes and reveal a novel, essential role of Sos2 in control of epidermal stem cell homeostasis.

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 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 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 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 Stem cell–driven lymphatic remodeling coordinates tissue regeneration

Science ◽  
2019 ◽  
Vol 366 (6470) ◽  
pp. 1218-1225 ◽  
Author(s):  
Shiri Gur-Cohen ◽  
Hanseul Yang ◽  
Sanjeethan C. Baksh ◽  
Yuxuan Miao ◽  
John Levorse ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Mouse Model ◽  
Hair Follicle ◽  
Tissue Regeneration ◽  
Wound Repair ◽  
Lymphatic Drainage ◽  
Tissue Growth ◽  
Niche Components

Tissues rely on stem cells (SCs) for homeostasis and wound repair. SCs reside in specialized microenvironments (niches) whose complexities and roles in orchestrating tissue growth are still unfolding. Here, we identify lymphatic capillaries as critical SC-niche components. In skin, lymphatics form intimate networks around hair follicle (HF) SCs. When HFs regenerate, lymphatic–SC connections become dynamic. Using a mouse model, we unravel a secretome switch in SCs that controls lymphatic behavior. Resting SCs express angiopoietin-like protein 7 (Angptl7), promoting lymphatic drainage. Activated SCs switch to Angptl4, triggering transient lymphatic dissociation and reduced drainage. When lymphatics are perturbed or the secretome switch is disrupted, HFs cycle precociously and tissue regeneration becomes asynchronous. In unearthing lymphatic capillaries as a critical SC-niche element, we have learned how SCs coordinate their activity across a tissue.

scholarly journals Migration of Melanoblasts into the Developing Murine Hair Follicle Is Accompanied by Transient c-Kit Expression

2002 ◽  
Vol 50 (6) ◽  
pp. 751-766 ◽  
Author(s):  
Eva M. J. Peters ◽  
Desmond J. Tobin ◽  
Natasha Botchkareva ◽  
Marcus Maurer ◽  
Ralf Paus
Keyword(s):  
Stem Cell ◽  
Hair Follicle ◽  
Stem Cell Factor ◽  
Mouse Skin ◽  
Dermal Papilla ◽  
Hair Follicles ◽  
Cell Populations ◽  
Outer Root Sheath ◽  
Hair Bulb ◽  
Root Sheath

Disruption of the c-Kit/stem cell factor (SCF) signaling pathway interferes with the survival, migration, and differentiation of melanocytes during generation of the hair follicle pigmentary unit. We examined c-Kit, SCF, and S100 (a marker for precursor melanocytic cells) expression, as well as melanoblast/melanocyte ultrastructure, in perinatal C57BL/6 mouse skin. Before the onset of hair bulb melanogenesis (i.e., stages 0–4 of hair follicle morphogenesis), strong c-Kit immunoreactivity (IR) was seen in selected non-mela-nogenic cells in the developing hair placode and hair plug. Many of these cells were S100-IR and were ultrastructurally identified as melanoblasts with migratory appearance. During the subsequent stages (5 and 6), increasingly dendritic c-Kit-IR cells successively invaded the hair bulb, while S100-IR gradually disappeared from these cells. Towards the completion of hair follicle morphogenesis (stages 7 and 8), several distinct follicular melanocytic cell populations could be defined and consisted broadly of (a) undifferentiated, non-pigmented c-Kit-negative melanoblasts in the outer root sheath and bulge and (b) highly differentiated melanocytes adjacent to the hair follicle dermal papilla above Auber's line. Widespread epithelial SCF-IR was seen throughout hair follicle morphogenesis. These findings suggest that melanoblasts express c-Kit as a prerequisite for migration into the SCF-supplying hair follicle epithelium. In addition, differentiated c-Kit-IR melanocytes target the bulb, while non-c-Kit-IR melanoblasts invade the outer root sheath and bulge in fully developed hair follicles.

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