Multi-potentiality of a new immortalized epithelial stem cell line derived from human hair follicles

Roh, Cecilia; Roche, Michael; Guo, Zhiru; Photopoulos, Christos; Qian, Tao; Lyle, Stephen

doi:10.1007/s11626-008-9084-2

Cited by 34 publications

(40 citation statements)

References 31 publications

(45 reference statements)

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“…Hair bulge is the niche for different type of stem cells 3,12 . Lyle and colleagues have shown isolation of human epithelial stem cells from hair bulge and these cells are multiple potent along the epithelial lineages 13 . Melanocyte precursors also reside in the hair bulge 3 .…”

Section: Discussionmentioning

confidence: 99%

Isolation and Culture of Neural Crest Stem Cells from Human Hair Follicles

Yang

2013

JoVE

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Hair follicles undergo lifelong growth and hair cycle is a well-controlled process involving stem cell proliferation and quiescence. Hair bulge is a well-characterized niche for adult stem cells . Hair follicles represent an accessible and rich source for different types of human stem cells. We and others have isolated neural crest stem cells (NCSCs) from human fetal and adult hair follicles 4,5 . These human stem cells are label-retaining cells and are capable of self-renewal through asymmetric cell division in vitro. They express immature neural crest cell markers but not differentiation markers. Our expression profiling study showed that they share a similar gene expression pattern with murine skin immature neural crest cells. They exhibit clonal multipotency that can give rise to myogenic, melanocytic, and neuronal cell lineages after in vitro clonal single cell culture. Differentiated cells not only acquire lineage-specific markers but also demonstrate appropriate functions in ex vivo conditions. In addition, these NCSCs show differentiation potential toward mesenchymal lineages. Differentiated neuronal cells can persist in mouse brain and retain neuronal differentiation markers. It has been shown that hair follicle derived NCSCs can help nerve regrowth, and they improve motor function in mice transplanted with these stem cells following transecting spinal cord injury 8 . Furthermore, peripheral nerves have been repaired with stem cell grafts 9 , and implantation of skin-derived precursor cells adjacent to crushed sciatic nerves has resulted in remyelination 10 . Therefore, the hair follicle/skin derived NCSCs have already shown promising results for regenerative therapy in preclinical models.Somatic cell reprogramming to induced pluripotent stem (iPS) cells has shown enormous potential for regenerative medicine. However, there are still many issues with iPS cells, particularly the long term effect of oncogene/virus integration and potential tumorigenicity of pluripotent stem cells have not been adequately addressed. There are still many hurdles to be overcome before iPS cells can be used for regenerative medicine. Whereas the adult stem cells are known to be safe and they have been used clinically for many years, such as bone marrow transplant. Many patients have already benefited from the treatment. Autologous adult stem cells are still preferred cells for transplantation. Therefore, the readily accessible and expandable adult stem cells in human skin/hair follicles are a valuable source for regenerative medicine. Video LinkThe video component of this article can be found at http://www.jove.com/video/3194/ Protocol 1. Preparation of Tissue Culture Plates 1. Coat each well with enough Poly-D-Lysine (PDL) to cover the bottom of the well. Allow the plates to dry in the hood. 2. After the wells are dry, rinse with sterile water, and aspirate. Allow the plates to dry in the hood. 3. When dry, coat with fibronectin (that was dissolved in biowhittaker water overnight at 37 °C at a concentration of 1 mg i...

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Section: Discussionmentioning

confidence: 99%

Isolation and Culture of Neural Crest Stem Cells from Human Hair Follicles

Yang

2013

JoVE

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“…K15 has, in recent years, gained considerable attention by virtue of its observed enrichment in the hair follicle bulge region where multipotential epidermal stem cells are located [17][18][19][20] and its expression by a subpopulation of epidermal cells that are thought to have stem cell characteristics [21][22][23]. Indeed, since its initial identification as a marker of hair follicle stem cells, use of K15 to identify epithelial stem cells after various isolation procedures has increased (e.g., [20,24,25]).…”

Section: Introductionmentioning

confidence: 99%

“…Indeed, since its initial identification as a marker of hair follicle stem cells, use of K15 to identify epithelial stem cells after various isolation procedures has increased (e.g., [20,24,25]). However, no studies have yet fully characterized K15 expression during normal epidermal development or repair to asses whether the expression profiles are consist with its assigned role in the stem cell compartment.…”

Section: Introductionmentioning

confidence: 99%

Re-Assessing K15 as an Epidermal Stem Cell Marker

Troy

Arabzadeh

Turksen

2011

Stem Cell Rev and Rep

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The intermediate filament keratin 15 (K15) is present in variable amounts in various stratified epithelia, but has also been reported to be a stem cell marker in the hair follicle. Using peptide specific antibodies, we evaluated the temporal and spatial distribution pattern of K15 expression/localization during normal epidermal development and initiation of hair follicle formation, and in the injured mature epidermis (e.g., during acute injury and repair and in tumorigenesis). During development, K15 expression is first localized to a subset of epidermal basal cells and the overlying periderm at E12.5, but its expression is seen throughout the basal layer by E15.5 and beyond. In hair follicle morphogenesis, initial peg formation occurs in a K15-null area at E14.5 and as peg elongation proceeds through to the mature hair follicle, K15 expression follows the leading edge with positive cells restricted to the outer root sheath. In an epidermal injury model, K15 is first up-regulated and associated with both the basal and suprabasal layers of the interfollicular epidermis then expression becomes sporadic and down-regulated before a basal layer-specific association is re-established in the repaired epidermis. During tumorigenesis, K15 is first mis-expressed, and is ultimately down-regulated. Our data suggest that K15 protein expression may reflect not only expression in a stem or progenitor cell subpopulation, but also reflects the activity and responsiveness of basal-like cells to loss of homeostasis of the epidermal differentiation program. Thus, the data suggest caution in using K15 alone to delineate epidermal stem cells, and underscore the need for further investigation of K15 and other markers in epidermal cell subpopulations.

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“…4 Several in vivo markers identify epidermal stem cells in both human and murine species, including CD34, a6-integrin, Keratin 14 (K14), Keratin 15 (K15), LGR5, LGR6, Sca-1, and Lrig1. 1,2,[4][5][6][7][8] Recent work by several groups has demonstrated the regenerative capabilities of these bulge stem cells. [9][10][11][12][13] Murine bulge cells expressing both CD34 and a6 are capable of regenerating new hair follicles within each hair cycle.…”

mentioning

confidence: 99%

Microfluidic Enrichment of Mouse Epidermal Stem Cells and Validation of Stem Cell Proliferation In Vitro

Zhu

Smith

Yarmush

et al. 2013

Tissue Engineering Part C: Methods

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Bulge stem cells reside in the lowest permanent portion of hair follicles and are responsible for the renewal of these follicles along with the repair of the epidermis during wound healing. These cells are identified by surface expression of CD34 and the a6-integrin. When CD34 and a6 double-positive cells are isolated and implanted into murine skin, they give rise to epidermis and hair follicle structures. The current gold standard for isolation of these stem cells is fluorescence-activated cell sorting (FACS) based on cell surface markers. Here, we describe an alternative method for CD34 bulge stem cell isolation: a microfluidic platform that captures stem cells based on cell surface markers. This method is relatively fast, requiring 30 min of time from direct introduction of murine skin tissue digestate into a two-stage microfluidic device to one-pass elution of CD34+ enriched cells with a purity of 55.8% -5.1%. The recovered cells remain viable and formed colonies with characteristic morphologies. When grown in culture, enriched cells contain a larger a6 + population than un-enriched cells.

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Multi-potentiality of a new immortalized epithelial stem cell line derived from human hair follicles

Cited by 34 publications

References 31 publications

Isolation and Culture of Neural Crest Stem Cells from Human Hair Follicles

Isolation and Culture of Neural Crest Stem Cells from Human Hair Follicles

Re-Assessing K15 as an Epidermal Stem Cell Marker

Microfluidic Enrichment of Mouse Epidermal Stem Cells and Validation of Stem Cell Proliferation In Vitro

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