Hair Follicle Bulge Research Articles

In Vitro differentiation of hair-follicle bulge stem cells into synaptophysin-expressing neurons: a potential new approach for neuro-regeneration.

Stem cells, particularly bulge hair follicle stem cells (HFSCs), have recently attracted significant interest due to their potential for tissue repair and regeneration. These cells, marked by their expression of Nestin (a neural stem cell marker), suggest the possibility of neural differentiation into neurons. This study investigated the use of retinoic acid (RA) and epidermal growth factor (EGF) to induce HFSC transformation into mature neurons, identified by synaptophysin expression. Rat whisker follicles were cultured in a medium suitable for HFSC survival and proliferation. Immunostaining techniques were used to identify HFSCs and assess their differentiation into neural cells. The addition of RA and EGF to the culture medium aimed to induce this differentiation. Findings demonstrate that HFSCs expressed Nestin, indicating their pluripotent nature. Treatment with RA and EGF resulted in synaptophysin expression, a marker of mature neurons, which was absent in the control group. However, this treatment group also displayed a decrease in the expression of other neural markers (βIII tubulin and NeuN). This study suggests that a combination of RA and EGF can accelerate HFSC differentiation into synaptophysin-positive cells in vitro. This research paves the way for further exploration of its potential application in neuro-regeneration.

Transcription factor KROX20 marks epithelial stem cells for hair follicle formation.

Epidermal stem cells control homeostasis and regeneration of skin and hair. In the hair follicle (HF) bulge of mammals, populations of slow-cycling stem cells regenerate the HF during cyclical rounds of anagen (growth), telogen (quiescence), and catagen (regression). Multipotent epidermal cells are also present in the HF above the bulge area, contributing to the formation and maintenance of sebaceous gland and upper and middle portions of the HF. Here, we report that the transcription factor Krox20 is enriched in an epidermal stem cell population located in the upper/ middle HF. Expression analyses and lineage tracing using inducible Krox20-CreERT showed that Krox20-lineage cells migrate out of this HF region and contribute to the formation of bulge in the HF, serving as ancestors of bulge stem cells. In vivo depletion of these cells arrests HF morphogenesis. This study identifies a novel marker for an epidermal stem cell population that is indispensable for hair homeostasis.

Upregulation of caveolae-associated structural proteins in the hair follicle bulge of lichen planopilaris and frontal fibrosing alopecia.

Lichen planopilaris (LPP) and frontal fibrosing alopecia (FFA) are primary cicatricial alopecia that cause a major impact on quality of life due to irreversible hair loss and symptoms as itching, burning and pain. They are characterized by permanent loss of hair follicle stem cells (HFSCs) by pathomechanisms still poorly understood, resulting in poor efficacy of currently available treatments. Caveolae are flask-shaped lipid rafts invaginated within the plasma membrane of multiple cell types. Although their role in the HF physiology and pathophysiology is relatively unknown, we have previously demonstrated that the primary structural component of caveolae (caveolin-1 or Cav1) is upregulated in FFA. Thus, we propose to investigate the expression and localization of caveolae-associated structural proteins (Cav1, Cav2, and Cavin-1) and HFSCs (identified by K15) in both LPP and FFA. We analyzed 4 patients with LPP biopsied in affected and non-affected (NA) scalp, 4 patients with FFA biopsied in affected scalp and 4 healthy controls. Affected scalp of LPP and FFA demonstrated increased levels of Cav1 and Cavin-1 compared with HC and LPP-NA. Moreover, Cav1, Cav2 and Cavin1 all exhibit high colocalization with K15 and their expression appears to be negatively correlated, supporting the hypothesis that these proteins are important players in LPP/FFA and may serve as therapeutic targets in future treatments.

In vitro Differentiation of Melanocyte Stem Cells Derived from Vitiligo Patients into Functional Melanocytes

BACKGROUND: Melanocyte stem cells (MelSCs) residing in the hair follicle bulge act as melanocyte reservoir for skin and hair, and may serve as an autologous source for treating vitiligo. Therefore, the study aimed to evaluate the in vitro differentiation ability of MelSCs derived from vitiligo patients into melanin-producing melanocytes for potential cellular therapy.METHODS: MelSCs from the vitiliginous (V-MelSCs), non-vitiliginous (NV-MelSCs) regions of vitiligo patients, as well as from control subjects (C-MelSCs) were established for evaluating their differentiation potential into melanin producing cells. The differentiation abilities were compared at the cellular and molecular levels. MelSCs were differentiated in vitro into induced-melanocytes (iMCs) by supplementing the culture medium with melanogenic factors. iMCs were analyzed by quantitative polymerase chain reaction (qPCR) for the expression of key melanogenic markers, including tyrosinase (TYR), tyrosinase-related protein 1 (TYRP1), dopachrome tautomerase (DCT), microphthalmia-associated transcription factor (MITF), c-KIT and S100. iMCs were also stained with L-DOPA to assess TYR activity in cells. Intracellular melanin content in iMCs was evaluated and compared among the vitiligo and control groups.RESULTS: MelSCs induced into iMCs displayed morphological changes with longer dendrites and prominent nuclei. iMCs stained positive for L-DOPA with an average intracellular melanin content of 30 pg/cell. iMCs expressed key melanogenic genes and the relative expression did not differ significantly among the groups.CONCLUSION: NV-MelSCs were unaltered by disease pathogenesis and capable of differentiating into melanocytes compared to V-MelSCs. Hence, these cells might offer a reliable source of melanocytes for vitiligo repigmentation therapy by autologous cellular transplantation.KEYWORDS: melanocyte stem cells, differentiation, melanocytes, vitiligo, in vitro

Piperine reduces hair oiliness by inhibiting adipogenesis of hair stem cells

Piperine, an alkaloid compound in black pepper (Piper nigrum), has beneficial bioactivities. Specifically, piperine inhibits adipogenesis in 3T3-L1 cells by suppressing the transcriptional activity of PPARγ. Control of hair oiliness, which is related to adipogenic regulation, is important to prevent hair loss. Excessive sebum from the sebaceous gland (SG) can cause acne, folliculitis, or irritated skin by clogging pores. To investigate the in vivo function of piperine in SG, we used mice fed a high-fat diet (HFD). The HFD increased the size and Oil Red O (ORO) staining intensity of SG, which were significantly reduced by piperine. The HFD also upregulated the expression of sebocyte-associated genes, including PPARγ target genes, an effect reversed by piperine. In CD34/CD49f double-positive hair follicle bulge stem cells isolated from mouse vibrissae, piperine inhibited cellular adipogenesis, likely via transcriptional repression of related genes. Furthermore, piperine reduced the thickness of subcutaneous fat. In human dermal papilla cells, piperine inhibited cellular adipogenesis, as shown by the reduction in ORO staining and the downregulation of PPARγ target genes. In conclusion, piperine can be used to reduce hair greasiness by suppressing adipogenesis in hair stem cells.

Alterations in epidermal stem cells within the pilosebaceous unit in atrophic acne scars.

Atrophic acne scarring is a common sequela of inflammatory acne, causing significant problems for affected patients. Although prolonged inflammation and subsequent aberrant tissue regeneration are considered the underlying pathogenesis, the role of epidermal stem cells, which are crucial to the regeneration of pilosebaceous units, remains unknown. To examine the changes occurring in epidermal stem cells in atrophic acne scars. Changes in collagen, elastic fibre and human leukocyte antigen (HLA)-DR expression were analysed in normal skin and inflammatory acne lesions at days 1, 3 and 7 after development. The expression of epidermal stem cell markers and proliferation markers was compared between normal skin and mature atrophic acne scar tissue. In acne lesions, inflammation had invaded into pilosebaceous units over time. Their normal structure had been destructed and replaced with a reduced amount of collagen and elastic fibre. Expression of stem cell markers including CD34, p63, leucine-rich repeat-containing G protein-coupled receptor (LGR)6 and LGR5, which are expressed in the interfollicular epidermis, isthmus and bulge of hair follicles, significantly decreased in atrophic acne scar tissue compared to normal skin. Epidermal proliferation was significantly reduced in scar tissue. These findings suggest that as inflammatory acne lesions progress, inflammation gradually infiltrates the pilosebaceous unit and affects the resident stem cells. This disruption impedes the normal regeneration of the interfollicular epidermis and adnexal structures, resulting in atrophic acne scars.

Distinct mechanisms for sebaceous gland self-renewal and regeneration provide durability in response to injury

Sebaceous glands (SGs) release oils that protect our skin, but how these glands respond to injury has not been previously examined. Here, we report that SGs are largely self-renewed by dedicated stem cell pools during homeostasis. Using targeted single-cell RNA sequencing, we uncovered both direct and indirect paths by which resident SG progenitors ordinarily differentiate into sebocytes, including transit through a Krt5+PPARγ+ transitional basal cell state. Upon skin injury, however, SG progenitors depart their niche, reepithelialize the wound, and are replaced by hair-follicle-derived stem cells. Furthermore, following targeted genetic ablation of >99% of SGs from dorsal skin, these glands unexpectedly regenerate within weeks. This regenerative process is mediated by alternative stem cells originating from the hair follicle bulge, is dependent upon FGFR2 signaling, and can be accelerated by inducing hair growth. Altogether, our studies demonstrate that stem cell plasticity promotes SG durability following injury.

Characterization of Epithelial Stem Cells and Mesenchymal Stem Cells from Human Hair Follicle

Hair follicle mesenchymal stem cells (HF-MSCs) and epithelial stem cells (HF-EpSCs) play a key role in hair growth and regeneration. The isolation, culture and characterization of HF-MSCs and HF-EpSCs will provide clues for in vitro tissue models and regenerative medicine applications. In this study, HF-MSCs and HF-EpSCs from the hair bulge were harvested using the tissue culture method. HF-MSCs exhibited a fibroblast shape and expressed highly the mesenchymal markers CD44, CD73, CD90 and CD105 and a lack of hematopoietic markers CD45, CD34, CD11b, CD19 and HLA-DR. They showed the potential for differentiation into adipogenic, osteogenic and chondrogenic lineages. HF-EpSCs possessed the keratinocyte shape and expressed typical markers for epithelial stem cells such as CD200, CK15 and CK19. The stemness marker CD49f was preferentially expressed in HF-EpSCs over HF-MSCs. Moreover, the expression of pluripotent factors including c-myc, oct-4, sox-2, klf-4 and nanog at the mRNA level was higher in HF-EpSCs compared to the expression in HF-MSCs. In conclusion, we successfully isolated mesenchymal and epithelial stem cells via culturing the hair follicle bulge tissues and preliminarily evaluated the stemness and plasticity of these two populations. This information will provide clues for further studies on hair regeneration in vitro and in vivo.

Sox9 regulates melanocytic fate decision of adult hair follicle stem cells

The bulge of hair follicles harbors Nestin+ (neural crest like) stem cells, which exhibit the potential to generate various cell types including melanocytes. In this study, we aimed to determine the role of Sox9, an important regulator during neural crest development, in melanocytic differentiation of those adult Nestin+ cells. Immunohistochemical analysis after conditional Sox9 deletion in Nestin+ cells of adult mice revealed that Sox9 is crucial for melanocytic differentiation of these cells and that Sox9 acts as a fate determinant between melanocytic and glial fate. A deeper understanding of factors that regulate fate decision, proliferation and differentiation of these stem cells provides new aspects to melanoma research as melanoma cells share many similarities with neural crest cells. In summary, we here show the important role of Sox9 in melanocytic versus glial fate decision of Nestin+ stem cells in the skin of adult mice.

1435 Enzymatic digestion of scalp hair follicle bulge allows to have more bulge-derived stem keratinocytes than explant isolation

1435 Enzymatic digestion of scalp hair follicle bulge allows to have more bulge-derived stem keratinocytes than explant isolation

Pigment cell progenitor heterogeneity and reiteration of developmental signaling underlie melanocyte regeneration in zebrafish.

Tissue-resident stem and progenitor cells are present in many adult organs, where they are important for organ homeostasis and repair in response to injury. However, the signals that activate these cells and the mechanisms governing how these cells renew or differentiate are highly context-dependent and incompletely understood, particularly in non-hematopoietic tissues. In the skin, melanocyte stem and progenitor cells are responsible for replenishing mature pigmented melanocytes. In mammals, these cells reside in the hair follicle bulge and bulb niches where they are activated during homeostatic hair follicle turnover and following melanocyte destruction, as occurs in vitiligo and other skin hypopigmentation disorders. Recently, we identified melanocyte progenitors in adult zebrafish skin. To elucidate mechanisms governing melanocyte progenitor renewal and differentiation we analyzed individual transcriptomes from thousands of melanocyte lineage cells during the regeneration process. We identified transcriptional signatures for progenitors, deciphered transcriptional changes and intermediate cell states during regeneration, and analyzed cell-cell signaling changes to discover mechanisms governing melanocyte regeneration. We identified KIT signaling via the RAS/MAPK pathway as a regulator of melanocyte progenitor direct differentiation and asymmetric division. Our findings show how activation of different subpopulations of mitfa-positive cells underlies cellular transitions required to properly reconstitute the melanocyte pigmentary system following injury.

Predominant expression of interleukin (IL)‐17 in chronic alopecia areata compared to IFN‐γ in pathogenic Th17 cells, tissue‐resident memory T cells and natural killer cells

AbstractBackgroundAlopecia areata (AA) is an organ‐specific autoimmune disease resulting from the attack of hair follicle (HF) autoantigens through a T‐cell‐mediated mechanism. If there is a depletion of mTregs in HFs, especially around both hair bulge and hair bulb, it could be related to patchy hair loss in the scalp and may affect AA pathogenesis.Objectiveswe investigated the possible contributory role of tissue‐resident memory T cells (TRMs) and memory regulatory T cells (mTregs), compared to cytotoxic T lymphocytes and Th17 lymphocytes, in the immunopathogenesis of chronic AA.MethodsThree hundred and sixty‐seven patients with AA who had biopsies performed in Dong‐A University Hospital between January 1994 and April 2019 were retrospectively reviewed. To investigate the expression of immunoregulatory molecules, we underwent double direct immunofluorescence with paraffin sections from nine AA patients under classified according to the histopathological grading of Uno and Orecchia's classification.ResultsThe number of lesional Foxp3+ Tregs was significantly decreased with an increase in the severity of histopathological gradings at both the hair bulge and hair bulb, in the following order: Type 1 > type 2 > type 3 AA lesions. The number of CD8+ CD69+ TRM cells at both the HF bulge and bulb was increased with the severity of histopathological grades. CD49a was not expressed in the hair bulge and bulb in any type of AA. As for the expression profile of effector T cells, interleukin (IL)‐17 was expressed in a denser pattern around the hair bulge with more severe histopathological grading, but IFN‐γ was expressed only at the hair bulge of type 1 AA. Lesional IL‐17 around the hair bulb also increased with the severity of histopathological grade. In contrast, IFN‐γ was expressed in the hair bulb only in type 1 AA.ConclusionsThe insidious destruction of hair bulge stem cells and hair bulb matrix stem cells, which is mediated by Th17 lymphocytes and cytotoxic T lymphocyte infiltration, results in more severe hair loss in patients with chronic AA. IL‐17 may play a more important role in the pathogenesis of chronic AA than IFN‐γ.

MicroRNA-148a Controls Epidermal and Hair Follicle Stem/Progenitor Cells by Modulating the Activities of ROCK1 and ELF5

Skin and hair development is regulated by complex programs of gene activation and silencing and microRNA-dependent modulation of gene expression to maintain normal skin and hair follicle development, homeostasis, and cycling. In this study, we show that miR-148a, through its gene targets, plays an important role in regulating skin homeostasis and hair follicle cycling. RNA and protein analysis of miR-148a and its gene targets were analyzed using a combination of invitro and invivo experiments. We show that the expression of miR-148a markedly increases during telogen (bulge and hair germ stem cell compartments). Administration of antisense miR-148a inhibitor into mouse skin during the telogen phases of the postnatal hair cycle results in accelerated anagen development and altered stem cell activity in the skin. We also show that miR-148a can regulate colony-forming abilities of hair follicle bulge stem cells as well as control keratinocyte proliferation/differentiation processes. RNA and protein analysis revealed that miR-148a may control these processes by regulating the expression of Rock1 and Elf5 invitro and invivo. These data provide an important foundation for further analyses of miR-148a as a crucial regulator of these genes target in the skin and hair follicles and its importance in maintaining stem/progenitor cell functions during normal tissue homeostasis and regeneration.

732 Treatment with cyclohexyl salicylate, an olfactory receptor 2A4/7 agonist, promotes human hair follicle growth and bulge stem cell progeny expansion

Topically applicable non-drugs that enhance the efficacy of available FDA-licensed drugs would be a welcome therapeutic addition in hair loss management. Since the olfactory receptor (OR) agonist, Sandalore, promotes human hair growth and reduces telogen effluvium, we have explored here whether other cosmetic OR ligands can unfold similar properties. We focused on OR2A4/7, since its stimulation promotes epidermal keratinocyte proliferation and differentiation. In situ hybridization showed that OR2A4/7 mRNA is widely expressed in the hair follicle (HF) epithelium, namely the outer root sheath (ORS) and hair matrix (HM). Yet, in freshly embedded human scalp skin, OR2A4/7 protein was mainly restricted to the infundibulum. However, OR2A4/7 protein became widely expressed in the ORS and HM during HF organ culture (OC), suggesting up-regulation of intrafollicular OR2A4/7 expression under tissue stress conditions. In scalp HF OC, the cosmetic OR2A4/7 agonist, cyclohexyl salicylate (CHS), delayed catagen development and tendentially increased HM proliferation. While CHS did not seem to impact on K15+ bulge stem cells, the % of CD34+ cells, i.e. their immediate progeny, was significantly increased in the suprabulbar ORS, as was the % of CD71+ transit amplifying cells (thought to derive from CD34+ cells) in the HM and suprabulbar ORS. Thus, stimulating OR2A4/7 via the non-drug CHS promotes hair growth and expands the progeny of K15+ stem cells, inviting the use of CHS as a novel cosmetic adjuvant treatment for hair loss disorders characterized by premature catagen development and a reduced capacity of K15+ stem cells to generate progeny, such as androgenetic alopecia.

Metformin Promotes Mechanical Stretch-Induced Skin Regeneration by Improving the Proliferative Activity of Skin-Derived Stem Cells.

BackgroundSkin expansion by mechanical stretch is an essential and widely used treatment for tissue defects in plastic and reconstructive surgery; however, the regenerative capacity of mechanically stretched skin limits clinical treatment results. Here, we propose a strategy to enhance the regenerative ability of mechanically stretched skin by topical application of metformin.MethodsWe established a mechanically stretched scalp model in male rats (n = 20), followed by their random division into two groups: metformin-treated (n = 10) and control (n = 10) groups. We measured skin thickness, collagen volume fraction, cell proliferation, and angiogenesis to analyze the effects of topical metformin on mechanically stretched skin, and immunofluorescence staining was performed to determine the contents of epidermal stem cells and hair follicle bulge stem cells in mechanically stretched skin. Western blot was performed to detect the protein expression of skin-derived stem cell markers.ResultsCompared with the control group, metformin treatment was beneficial to mechanical stretch-induced skin regeneration by increasing the thicknesses of epidermis (57.27 ± 10.24 vs. 31.07 ± 9.06 μm, p < 0.01) and dermis (620.2 ± 86.17 vs. 402.1 ± 22.46 μm, p < 0.01), number of blood vessels (38.30 ± 6.90 vs. 17.00 ± 3.10, p < 0.01), dermal collagen volume fraction (60.48 ± 4.47% vs. 41.28 ± 4.14%, p < 0.01), and number of PCNA+, Aurora B+, and pH3+ cells. Additionally, we observed significant elevations in the number of proliferating hair follicle bulge stem cells [cytokeratin (CK)15+/proliferating cell nuclear antigen (PCNA)+] (193.40 ± 35.31 vs. 98.25 ± 23.47, p < 0.01) and epidermal stem cells (CK14+/PCNA+) (83.00 ± 2.38 vs. 36.38 ± 8.96, p < 0.01) in the metformin-treated group, and western blot results confirmed significant increases in CK14 and CK15 expression following metformin treatment.ConclusionTopical application of metformin enhanced the regenerative capacity of mechanically stretched skin, with the underlying mechanism possibly attributed to improvements in the proliferative activity of skin-derived stem cells.

The Rho guanosine nucleotide exchange factors Vav2 and Vav3 modulate epidermal stem cell function

It is known that Rho GTPases control different aspects of the biology of skin stem cells (SSCs). However, little information is available on the role of their upstream regulators under normal and tumorigenic conditions in this process. To address this issue, we have used here mouse models in which the activity of guanosine nucleotide exchange factors of the Vav subfamily has been manipulated using both gain- and loss-of-function strategies. These experiments indicate that Vav2 and Vav3 regulate the number, functional status, and responsiveness of hair follicle bulge stem cells. This is linked to gene expression programs related to the reinforcement of the identity and the quiescent state of normal SSCs. By contrast, in the case of cancer stem cells, they promote transcriptomal programs associated with the identity, activation state, and cytoskeletal remodeling. These results underscore the role of these Rho exchange factors in the regulation of normal and tumor epidermal stem cells.

Mapping the Lipids of Skin Sebaceous Glands and Hair Follicles by High Spatial Resolution MALDI Imaging Mass Spectrometry.

Matrix-assisted laser desorption/ionization (MALDI) imaging mass spectrometry (IMS) is a technology that utilizes the high sensitivity and specificity of mass spectrometry, combined with a high spatial resolution to characterize the molecular species present in skin tissue. In this article, we use MALDI IMS to map specific lipids characteristic of two important skin appendages in minipig skin: the sebaceous glands and hair follicles. A set of specific lipid markers linked to the synthesis of sebum, stages of sebum production, and the secretion of sebum for two different sebaceous gland subzones, the peripheral and central necrotic, were identified. Furthermore, biochemical pathway analysis of the identified markers provides potential drug-targeting strategies to reduce sebum overproduction in pathological conditions. In addition, specific lipid markers characteristic of the different layers in the hair follicle bulge area, including the outer root sheath, the inner root sheath, and the medulla that are associated with the growth cycles of the hair, were determined. This research highlights the ability of MALDI IMS to link a molecular distribution not only to the morphological features in skin tissue but to the physiological state as well. Thus, this platform can provide a basis for the investigation of biochemical pathways as well as the mechanisms of disease and pharmacology in the skin, which will ultimately be critical for drug discovery and the development of dermatology-related illnesses.

Hair Graying Regulators Beyond Hair Follicle.

Hair graying is an interesting physiological alteration associated with aging and certain diseases. The occurrence is due to depigmentation of the hair caused by depletion and dysfunction of melanocyte stem cells (MeSCs). However, what causes the depletion and dysfunction of MeSCs remains unclear. MeSCs reside in the hair follicle bulge which provides the appropriate niche for the homeostasis of various stem cells within hair follicle including MeSCs. In addition to local signaling from the cells composed of hair follicle, emerging evidences have shown that nerves, adipocytes and immune cells outside of hair follicle per se also play important roles in the regulation of MeSCs. Here, we review the recent studies on different cells in the MeSCs microenvironment beyond the hair follicle per se, discuss their function in regulating hair graying and potentially novel treatments of hair graying.

Differences in anatomical area-specific wound healing in hidradenitis suppurativa/acne inversa after surgery

Hidradenitis suppurativa/acne inversa is an inflammatory, debilitating disease for which wide local excision of the affected area with secondary wound healing is considered the treatment of first choice for the inactive scarring form or after adequate anti-inflammatory medical treatment. In this study, we aimed to assess the duration of complete secondary wound healing after surgical intervention for hidradenitis suppurativa/acne inversa. Twenty-three surgical procedures in 17 consecutive patients (eight female, nine male) were evaluated for duration of secondary wound healing at axillary or anogenital/inguinal sites. To investigate the contribution of hair follicle bulge progenitor cells in wound re-epithelialization, tissue samples of lesional and perilesional skin were analysed for expression of the stem cell marker, cytokeratin 15 (CK15), and CD200, a marker for human follicular stem cells that resides in the bulge area. Initial wound size did not differ significantly between surgical wounds in the axillary (mean: 30.0 cm2 ± 5.4) and anogenital/inguinal (mean: 35.3 cm2 ± 5.7) region. However, healing time to complete wound closure was almost twice as fast in the anogenital/inguinal (mean: 132 days ± 10.4) than axilla area (mean: 254 days ± 39.1; p < 0.01). The accelerated wound healing in the anogenital/inguinal region was accompanied by significantly enhanced CK15 and CD200 expression, compared to axillary wounds (p < 0.05). The anogenital/inguinal region showed significantly faster secondary wound healing after surgical intervention for hidradenitis suppurativa/acne inversa compared to axillary wounds. We suspect differences in pilosebaceous unit density and thus hair follicle progenitor cells (as mirrored by CK15 and CD200 expression) to be the main driver behind this finding.

Influence of the Neural Crest Derived Stem Cells to Optic Nerve Regeneration After Its Experimental Injury

Purpose: Orbital trauma is a challenging problem due to such severe sequel as diplopia, decrease of vision or eye motility disorder. However, the conditions of orbital soft tissue content still become underestimated. The aim of this study was to investigate structural changes in the rat optic nerve after experimental injury followed by treatment with stem cells. Materials and Ьethods: An experimental model of injury to the orbital soft tissue content in the rat was developed. Forty Wistar rats maintained under daylight were divided into two equal experimental groups. Unlike the rats of Group I, in rats of Group II, the site of injury to the orbital soft tissue mass received postnatal multipotent stem cells, epidermal neural crest stem cells (NCSCs) derived from the bulge of hair follicles. Results: Comparing the number of glial cells per certain area of the slice (NC) between group І and site without injury (control) after 3 week of observation, it was higher in group I more than 258.8% (p &lt; 0.0001) and on 272.4% in group II (p &lt; 0.0001). After 6 weeks NC in group I was higher than at previous terms: more then 128.9% (р &lt; 0.0001). At the same, NC in group II was higher comparing with previous terms only on 17.1% (р = 0.0212). Between the animals of group I at terms of 12 and 24 weeks NC high and wasn’t significantly differ between this terms of observation (ANOVA p = 0.4379). In contrast, NC in group II stopped rising between 6 and 12 weeks demonstrating statistical equality (p = 0.4563). Conclusions: It can be assumed that the application of mesenchymal stem cells, derivates of the neural crest, after the experimental orbital trauma, stimulates a recovery of the optic nerve. Further studies should be performed to more deeply discover the neural crest derived stem cell populations, ivoleved into recovery of damaged optic nerves.