Cystine-thiamin-containing hair-growth formulation modulates the response to UV radiation in an in vitro model for growth-limiting conditions of human keratinocytes

Hengl, Thomas; Herfert, Jörn; Soliman, Alexander; Schlinzig, Kim; Trüeb, Ralph M.; Abts, Harry F.

doi:10.1016/j.jphotobiol.2018.09.005

Cited by 12 publications

(10 citation statements)

References 26 publications

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“…Applying growthlimiting conditions to these cells allowed us to test the impact of the hair-growth-promoting combination and obtain hints on basic cellular processes that might be involved in improving hair-growth. Consistent with the NHEK-based study of Hengl et al, 10 measuring metabolic activity and proliferation of HHFKs cultivated in the minimal growth system revealed reduced cell activity. In the clinics, it is believed that diminished hair-growth is correlated to a reduced activity of hair follicle cells.…”

Section: Discussionsupporting

confidence: 84%

“…In this study, the impact of a hair-growth-promoting, L-cystine-containing combination on cellular processes was investigated by employing a growth limiting in vitro system, which was published recently. 10 The selected core compounds of the hair-growthpromoting combination (Panto[vi]gar ® ) L-cystine, thiamine, calcium D-pantothenate, and folic acid (as an assumed metabolite of PABA) were the main focus of this work. While in the study of Hengl et al the minimal growth system was used with normal human epidermal keratinocytes (NHEKs), 10 we evaluated the compound effects using HHFKs, which represent a mixed population of keratinocytes derived from the hair follicle, aiming to use a simplified in vitro model, which is closer to the hair follicle physiology.…”

Section: Discussionmentioning

confidence: 99%

“…10 The selected core compounds of the hair-growthpromoting combination (Panto[vi]gar ® ) L-cystine, thiamine, calcium D-pantothenate, and folic acid (as an assumed metabolite of PABA) were the main focus of this work. While in the study of Hengl et al the minimal growth system was used with normal human epidermal keratinocytes (NHEKs), 10 we evaluated the compound effects using HHFKs, which represent a mixed population of keratinocytes derived from the hair follicle, aiming to use a simplified in vitro model, which is closer to the hair follicle physiology. Applying growthlimiting conditions to these cells allowed us to test the impact of the hair-growth-promoting combination and obtain hints on basic cellular processes that might be involved in improving hair-growth.…”

Section: Discussionmentioning

confidence: 99%

“…IC serves as an in vitro correlate of the oral formulation Panto[vi]gar ® , which was developed depending on the expected systemic bioavailability at the hair follicle and the usability of compounds in an in vitro cell culture system. 10 The following experiments for characterization of compound effects were carried out after an incubation time of 72 h.…”

Section: Cell Culture and Treatmentmentioning

confidence: 99%

“…An established in vitro growth-limiting system, which mimics the reduced activity of keratinocytes associated with diminished hair-growth, 10 was employed to investigate the influence of hair-growth-promoting combinations on cellular processes, aiming to elucidate the compound effects at a molecular level. The minimal growth medium (MGM) in this culture system omits all compounds provided by a marketed hair-growth formulation.…”

Section: Phenotypic Characterization Of Hhfks In a Minimal Growth Systemmentioning

confidence: 99%

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<p>L-Cystine-Containing Hair-Growth Formulation Supports Protection, Viability, and Proliferation of Keratinocytes</p>

Riegel

Hengl

Krischok

et al. 2020

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Purpose: Clinical studies have confirmed that the hair-growth-promoting effect of approved oral drug combinations is beneficial for the treatment of diffuse telogen effluvium, which is characterized by the excessive loss of telogen club hairs. Since data elucidating the mode of action of such combinations are limited, our study focused on the identification of cellular processes potentially supporting the treatment of hair loss. Materials and Methods: A minimal growth culture system (MGM) was used to mimic in vitro the reduced activity of human hair follicular keratinocytes (HHFKs). The effect of four core compounds (L-cystine, thiamine, calcium D-pantothenate, and folic acid) of a marketed oral combination (Panto[vi]gar ®), which are approved for the treatment of diffuse hair loss, was examined by comparing HHFKs cultured either with or without the compounds. After determining their impact on metabolic activity and proliferation, we conducted a comparative whole-genome gene expression study with subsequent functional grouping of differentially expressed genes to identify cellular processes influenced by the tested compounds. Results: The four core compounds of an oral hair-growth formulation enhanced proliferation and metabolic activity of HHFKs compared to HHFKs cultivated in MGM only. Functional grouping of differentially expressed genes confirmed the regulation of cell cycle-/proliferation-associated genes (cdk1, HJURP) and revealed regulation of cell death-and oxidative stress-associated gene groups. A supportive effect of the compounds on cell viability was demonstrated by lower sensitivity to solar-simulated UV-radiation and increased protection against oxidative stress. We established a central role for L-cystine, as changes in the expression of the anti-oxidative gene hmox1 were L-cystine-dependent. However, to reach a maximal stimulating effect on proliferation, the combination of all four compounds was necessary. Conclusion: The tested compound combination had positive effects on metabolic activity, cell viability, and proliferation of keratinocytes. Furthermore, this study suggested that L-cystine primarily contributes to the observed protection against endogenous oxidative stress.

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Section: Discussionsupporting

confidence: 84%

Section: Discussionmentioning

confidence: 99%