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L-Cystine-Containing Hair-Growth Formulation Supports Protection, Viability, and Proliferation of Keratinocytes

Authors Riegel K, Hengl T, Krischok S, Schlinzig K, Abts HF

Received 17 April 2020

Accepted for publication 5 June 2020

Published 3 August 2020 Volume 2020:13 Pages 499—510

DOI https://doi.org/10.2147/CCID.S254720

Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 2

Editor who approved publication: Dr Jeffrey Weinberg


Kristina Riegel,1,2 Thomas Hengl,2 Saskia Krischok,2,3 Kim Schlinzig,2 Harry F Abts2

1Cell Biology Unit, University Medical Center Mainz, Mainz 55131, Germany; 2Pharmaceutical Development, Merz Pharmaceuticals GmbH, Frankfurt Am Main 60438, Germany; 3Co.faktor GmbH, Berlin 10178, Germany

Correspondence: Harry F Abts
Merz Pharmaceuticals GmbH, 60438, Frankfurt Am Main, Alfred-Wegener-Straße 2, FIZ 2, F08.10.014, Frankfurt Am Main 60438, Germany
Tel +49 69 15 03 1324
Fax +49 69 15 03 9152
Email Harry.Abts@merz.com

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.

Keywords: telogen effluvium, protection, genetic analysis, keratinocytes, oxidative stress

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