Expression of Kruppel-Like Factor KLF4 in Mouse Hair Follicle Stem Cells Contributes to Cutaneous Wound Healing

Objective: An appropriate source of adult stem cells for therapeutic use is stem cells deriving from the hair follicle bulge. Following injury, ischaemic tissues produce a variety of cytokines and growth factors that are essential for tissue repair. This study sought to investigate the temporal effects of hair follicle bulge stem cells (HFSCs) on cutaneous wound healing in rats using the SDF-1α/CXCR4 axis. Method: HFSCs obtained from rat vibrissa, labeled with DiI and then special markers, were detected using flow cytometry. The animals were divided into five groups: control (non-treated, n=18), sham (PBS, n=18), AMD (treated with AMD3100, n=18), HFSC + AMD (treated with HFSCs + AMD3100, n=18) and HFSC (treated with HFSCs, n=18). A full-thickness excisional wound model was created and DiI-labeled HFSCs were injected around the wound bed. Wound healing was recorded with digital photographs. The animals were sacrificed 3, 7 and 14 days after the surgery and were used for histological (H&E, Masson's trichrome staining) and molecular (ELISA and q-PCR) assays. Results: The flow cytometry results demonstrated that HFSCs were CD34-positive, nestin-positive, but Kr15-negative. The morphological analysis of the HFSC-treated wounds showed accelerated wound closure. The histological analysis of the photomicrographs exhibited more re-epithelialisation and dermal structural regeneration in the HFSC-treated wounds compared with the control group. In the HFSC + AMD group, the histological parameters improved on the same days, but showed a significant decrease compared with the HFSC group in all the days assayed. In the AMD group, there was a significant reduction in the noted parameters. qRT-PCR and ELISA showed a high expression level of SDF-1α, CXCR4 and VEGFR-2 in the HFSC-treated wounded skin tissue, but the expression of CXCR4 and VEGFR-2 showed a significant reduction in the HFSC + AMD group compared with the HFSC group. Conclusions: Based on the findings of this study, HFSC transplantation affects wound closure parameters and the expression of SDF-1α and CXCR4. As the SDF-1α expression level increases in the injured area, the HFSCs contribute to wound repair through the SDF-1α/CXCR4 axis. This result is extremely valuable because it raises the possibility of wounds healed by isolating autologous HFSCs from the patient.

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Extracellular caspase-1 regulates hair follicle stem cell migration during wound-healing

10.1101/548529 ◽

2019 ◽

Author(s):

Subhasri Ghosh ◽

Akhil SHP Ananthan ◽

Sunny Kataria ◽

Neha Pincha ◽

Abhik Dutta ◽

...

Keyword(s):

Stem Cells ◽

Wound Healing ◽

Stem Cell ◽

Hair Follicle ◽

Healing Process ◽

Environmental Cues ◽

Macromolecular Complex ◽

Caspase 1 ◽

Hair Follicle Stem Cells ◽

Follicle Stem Cells

AbstractMigration of stem cells from one niche to another is a fundamental behavior observed during tissue morphogenesis, homeostasis, and repair 1. A common thread running throughout these phenomena is the ability of stem cells to sense their environmental cues that, in turn, regulate their spatiotemporal localization with amazing precision. Perturbations of such cellular responses underlie a spectrum of pathologies ranging from developmental defects, tumor metastasis and ineffective wound closure 2,3. In somatic tissues, the wound-healing process is a paradigm of the directed migration of various stem cell pools to the site of injury where they differentiate to replenish lost or damaged cells. While there has been substantial investment and progress in understanding the lineage trajectory of stem cells once they reach their destination, comparatively little is understood regarding the mechanisms guiding their chemotactic journey to the wound site. In the context of the skin, it has been shown nearly two decades ago that wounding activates various local epithelial stem cell pools, including multipotent hair follicle stem cells, to infiltrate the epidermis where they participate in the reconstruction of the damaged tissue 4,5. However, elucidation of the environmental cues that coax these cells out of their hair follicle niche to the damaged epidermis has proven to be an intractable problem to solve. Using both an excisional wound and genetic mouse models of wound healing, we discovered that wounded keratinocytes secrete the enzyme Caspase-1. This protein is classically known as a critical component of the cytosolic macromolecular complex called an inflammasome that mediates the unconventional secretion of various cytokines including IL-1a 6. Surprisingly, we find that the released caspase-1 itself has a non-canonical role in the extracellular milieu. Through the Caspase Activation Recruitment Domain (CARD) of caspase-1, this protein is sufficient to initiate chemotaxis of hair follicle stem cells into the epidermis. The secretion of caspase-1 has also been documented in many other pathological scenarios7,8 and we observed that the migration of HFSCs into the epidermis following UV irradiation of the skin is also caspase-1 dependent. Uncovering this novel function of Caspase-1 facilitates a deeper understanding of the mechanistic basis of the epithelial hyperplasia found to accompany numerous inflammatory skin diseases.

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Effects of Hair Follicle Stem Cells on Partial-Thickness Burn Wound Healing and Tensile Strength

Iranian Biomedical Journal ◽

10.29252/ibj.24.2.99 ◽

2020 ◽

Vol 24 (2) ◽

pp. 99-109 ◽

Cited By ~ 2

Author(s):

Azar Babakhani ◽

Malihe Nobakht ◽

Hamidreza Pazoki Torodi ◽

Mostafa Dahmardehei ◽

Paria Hashemi ◽

...

Keyword(s):

Stem Cells ◽

Wound Healing ◽

Tensile Strength ◽

Hair Follicle ◽

Burn Wound ◽

Burn Wound Healing ◽

Partial Thickness ◽

Partial Thickness Burn ◽

Hair Follicle Stem Cells ◽

Follicle Stem Cells

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Single-Cell Transcriptomics of Traced Epidermal and Hair Follicle Stem Cells Reveals Rapid Adaptations during Wound Healing

Cell Reports ◽

10.1016/j.celrep.2018.09.059 ◽

2018 ◽

Vol 25 (3) ◽

pp. 585-597.e7 ◽

Cited By ~ 53

Author(s):

Simon Joost ◽

Tina Jacob ◽

Xiaoyan Sun ◽

Karl Annusver ◽

Gioele La Manno ◽

...

Keyword(s):

Stem Cells ◽

Wound Healing ◽

Single Cell ◽

Hair Follicle ◽

Hair Follicle Stem Cells ◽

Follicle Stem Cells

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Participation of Somatic Stem Cells, Labeled by a Unique Antibody (A3) Recognizing Both N-glycan and Peptide, to Hair Follicle Cycle and Cutaneous Wound Healing in Rats

International Journal of Molecular Sciences ◽

10.3390/ijms21113806 ◽

2020 ◽

Vol 21 (11) ◽

pp. 3806

Author(s):

Chisa Katou-Ichikawa ◽

Hironobu Nishina ◽

Miyuu Tanaka ◽

Shigeo Takenaka ◽

Takeshi Izawa ◽

...

Keyword(s):

Stem Cells ◽

Wound Healing ◽

Connective Tissue ◽

Hair Follicle ◽

Mesenchymal Cells ◽

Cutaneous Wound Healing ◽

Somatic Stem Cells ◽

Cutaneous Wound ◽

Hair Follicle Cycle ◽

Connective Tissue Sheath

A monoclonal antibody (A3) was generated by using rat malignant fibrous histiocytoma (MFH) cells as the antigen. Generally, MFH is considered to be a sarcoma derived from undifferentiated mesenchymal cells. Molecular biological analyses using the lysate of rat MFH cells revealed that A3 is a conformation specific antibody recognizing both N-glycan and peptide. A3-labeled cells in bone marrow were regarded as somatic stem cells, because the cells partly coexpressed CD90 and CD105 (both immature mesenchymal markers). In the hair follicle cycle, particularly the anagen, the immature epithelial cells (suprabasal cells) near the bulge and some immature mesenchymal cells in the disassembling dermal papilla and regenerating connective tissue sheath/hair papilla reacted to A3. In the cutaneous wound-healing process, A3-labeled epithelial cells participated in re-epithelialization in the wound bed, and apparently, the labeled cells were derived from the hair bulge; in addition, A3-labeled immature mesenchymal cells in the connective tissue sheath of hair follicles at the wound edge showed the expansion of the A3 immunolabeling. A3-labeled immature epithelial and mesenchymal cells contributed to morphogenesis in the hair cycle and tissue repair after a cutaneous wound. A3 could become a unique antibody to identify somatic stem cells capable of differentiating both epithelial and mesenchymal cells in rat tissues.

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