Poor Capability of 3D-Cultured Adipose-Derived Stem Cells to Induce Hair Follicles in Contrast to 3D-Cultured Dermal Papilla Cells

Seo, Changhoon; Kwack, Mi Hee; Lee, Soo−Hong; Kim, Moon Kyu; Kim, Jung Chul; Sung, Young Kwan

doi:10.5021/ad.2016.28.5.662

Cited by 8 publications

(10 citation statements)

References 10 publications

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“…6B; i). This result is similar to previous report that human ASCs at p3 did not make hair sheath in hair reconstitution assay [9]. Histological staining revealed that hair follicle-like structure was observed under the hypodermis of tfASCs-injected mice, and was positive for cytokeratin 5 (K5) which is expressed on basal cell of the epidermis ( Fig.…”

Section: Tfascs Can Regenerate Hair Follicle In a Hair Reconstitutionsupporting

confidence: 92%

“…Preconditioning of ASCs using LL-37 also enhanced the hairregenerative potential of ASCs in an animal model [8]. However, Seo et al reported that three-dimensional (3D)-cultured human ASCs were inferior at inducing hair follicles compared with 3Dcultured human DP cells [9]. In addition, there is minimal evidence regarding a method of differentiating ASCs into DP cells.…”

Section: Introductionmentioning

confidence: 99%

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Generation of trichogenic adipose-derived stem cells by expression of three factors

Choi

Kim³

et al. 2018

Journal of Dermatological Science

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Collectively, these results indicate that 1) tfASCs have similar characteristics as DP cells, 2) tfASCs have enhanced hair-regenerative potential compared with ASCs, and 3) tfASCs even at late passage can make new hair follicles in a hair reconstitution assay. Because DP cells are difficult to isolate/expand and ASCs have low hair inductivity, tfASCs and tfASC-CM are clinically good candidates for hair regeneration.

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Section: Tfascs Can Regenerate Hair Follicle In a Hair Reconstitutionsupporting

confidence: 92%

Section: Introductionmentioning

confidence: 99%

Generation of trichogenic adipose-derived stem cells by expression of three factors

Choi

Kim³

et al. 2018

Journal of Dermatological Science

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“…15 While ADSCs exhibited hair growth-promoting effects in vivo, their hair neogenesis potential was inferior to that of DPCs. 16,17 Hypoxia increases proliferation and secretion of diverse growth factors that enhance ADSCsʼ hair growth-promoting effects. 18 Upton et al reported that 21% O 2 increases oxidative stress in DPCs, whereas hypoxia (2% O 2 ) maintains their healthy, spindle-like morphology and promotes increased proliferation and migration.…”

Section: Discussionmentioning

confidence: 99%

“…We previously demonstrated that hypoxia increases proliferation and migration of adipose‐derived mesenchymal stem cells (ADSCs) via generation of low concentrations of reactive oxygen species (ROS) . While ADSCs exhibited hair growth‐promoting effects in vivo , their hair neogenesis potential was inferior to that of DPCs . Hypoxia increases proliferation and secretion of diverse growth factors that enhance ADSCsʼ hair growth‐promoting effects .…”

mentioning

confidence: 99%

Hypoxia improves hair inductivity of dermal papilla cells via nuclearNADPHoxidase 4‐mediated reactive oxygen species generation'

Zheng¹,

Jang²,

Choi

et al. 2019

Br J Dermatol

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Summary Background Dermal papilla cells (DPCs) play a key role in hair regeneration and morphogenesis. Therefore, tremendous efforts have been made to promote DPC hair inductivity. Objectives The aim of this study was to investigate the mitogenic and hair inductive effects of hypoxia on DPCs and examine the underlying mechanism of hypoxia‐induced stimulation of DPCs. Methods DPCs' hair inductivity was examined under normoxia (20% O2) and hypoxia (2% O2). Results Hypoxia significantly increased the proliferation and delayed senescence of DPCs via Akt phosphorylation and downstream pathways. Hypoxia upregulated growth factor secretion of DPCs through the mitogen‐activated protein kinase pathway. Hypoxia‐preconditioned DPCs induced the telogen‐to‐anagen transition in C3H mice, and also enhanced hair neogenesis in a hair reconstitution assay. Injected green fluorescent protein‐labelled DPCs migrated to the outer root sheath of the hair follicle, and hypoxia‐preconditioning increased survival and migration of DPCs in vivo. Conditioned medium obtained from hypoxia increased the hair length of mouse vibrissa follicles via upregulation of alkaline phosphatase, vascular endothelial growth factor, and glial cell line‐derived neurotrophic factor. We examined the mechanism of this hypoxia‐induced stimulation, and found that reactive oxygen species (ROS) play a key role. For example, inhibition of ROS generation by N‐acetylcysteine or diphenyleneiodonium treatment attenuated DPCs' hypoxia‐induced stimulation, but treatment with ROS donors induced mitogenic effects and anagen transition. NADPH oxidase 4 is highly expressed in the DPC nuclear region, and NOX4 knockout by CRISPR‐Cas9 attenuated the hypoxia‐induced stimulation of DPCs. Conclusions Our results suggest that DPC culture under hypoxia has great advantages over normoxia, and is a novel solution for producing DPCs for cell therapy. Whatʼs already known about this topic? Dermal papilla cells (DPCs) play a key role in hair regeneration and morphogenesis, but they are difficult to isolate and expand for use in cell therapy. Tremendous efforts have been made to increase proliferation of DPCs and promote their hair formation ability. What does this study add? Hypoxia (2% O2) culture of DPCs increases proliferation, delays senescence and enhances hair inductivity of DPCs. Reactive oxygen species play a key role in hypoxia‐induced stimulation of DPC. What is the translational message? Preconditioning DPCs under hypoxia improves their hair regenerative potential, and is a novel solution for producing DPCs for cell therapy to treat hair loss.

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“…Unfortunately, the studies proved that the two-dimensional (2D) culture of the papilla cells lose their ability to form the hair (trichogenicity) and require a spheroidal form (3D) in culture [ 50 , 51 ], Table 1 .…”

Section: Alopeciamentioning

confidence: 99%

The Use of Adipose-Derived Stem Cells in Selected Skin Diseases (Vitiligo, Alopecia, and Nonhealing Wounds)

Owczarczyk‐Saczonek

Wociór

Placek

et al. 2017

Stem Cells International

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The promising results derived from the use of adipose-derived stem cells (ADSCs) in many diseases are a subject of observation in preclinical studies. ADSCs seem to be the ideal cell population for the use in regenerative medicine due to their easy isolation, nonimmunogenic properties, multipotential nature, possibilities for differentiation into various cell lines, and potential for angiogenesis. This article reviews the current data on the use of ADSCs in the treatment of vitiligo, various types of hair loss, and the healing of chronic wounds.

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Poor Capability of 3D-Cultured Adipose-Derived Stem Cells to Induce Hair Follicles in Contrast to 3D-Cultured Dermal Papilla Cells

Cited by 8 publications

References 10 publications

Generation of trichogenic adipose-derived stem cells by expression of three factors

Generation of trichogenic adipose-derived stem cells by expression of three factors

Hypoxia improves hair inductivity of dermal papilla cells via nuclearNADPHoxidase 4‐mediated reactive oxygen species generation'

The Use of Adipose-Derived Stem Cells in Selected Skin Diseases (Vitiligo, Alopecia, and Nonhealing Wounds)

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