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Dermo-cosmetics

Sebocyte models and acne

Sebocytes are the major cells within sebaceous glands. These glands are localized within the derm, but belong to the epiderm and are usually associated with an hair follicle. They consists in a secretory compartment composed of berry-like structures, the acini, connected to a common excretory duct. Sebum, the product of sebocyte activity, is hence secreted to the skin surface through this duct. Sebum helps to maintain skin lubrication and protect it against water loss, as well as exhibiting anti-oxydant and anti-microbial properties. Perturbations in sebum production and quality are involved in the pathogenesis of various skin diseases, among which the most prominent is acne vulgaris. Acne is estimated to affect approximately 85% of teenagers worldwide, and 10-40% of adults according to age group and sex. Because of its marked effect on the skin and the face, it can profoundly impact quality of life and well-being. Over the years, multiple causes have been identified for the development of acne, among which excess sebum production (Makrantonaki, Ganceviciene, & Zouboulis, 2011). Both genetic and environmental causes can be responsible for over-production of sebum, leading to acne (Figure 1).

Figure 1 An overview of the different factors responsible for excess sebum production and development of acne.

Since sebum originate from sebocytes, this cell type has been extensively studied over the past decades, through the use of different cellular models (Xia, Zouboulis, & Ju, 2009). In the early 1980’s, rat preputial sebocytes were initially used. However, acne is a human disease, and sebum composition is species specific. Next, primary cultures of human sebocytes were established, but the technic is challenging, and yields limited. In the late 1990’s, several immortalized human sebocyte cell lines were derived: these cells led to important advances in the understanding of the biology of sebocytes. However, they did not usually respond to androgen stimulation, and more importantly they displayed abnormal karyotypes. Recently, Phenocell has developed innovative protocols for the production of sebocytes from human induced pluripotent stem cells (hiPSC). hiPSC derived sebocytes recapitulate key functional responses, including to androgen induction, while having a normal karyotype. In addition, thanks to hiPSC technology, they are available in unlimited quantity and from a range of ethnic donors (Caucasian, Asian and African). Interestingly, hiPSC derived sebocytes of African origin produce significantly more lipid than their Caucasian and Asian counterparts (see figure 2). These results are in line with in vivo data indicating higher lipid levels in skin of African origin (Pappas, Fantasia, & Chen, 2013). They suggest that it might be possible to model ethnic differences related to skin lipid production in vitro using hiPSC derived sebocytes.

 

Figure 2 Lipid level quantification in hiPSC derived sebocytes from different ethnic donors

 

In conclusion, while sebocytes are of key interest for studies revolving around seborrhea and acne, research into these areas was limited by cellular models displaying incomplete phenotypes or technical challenges. hiPSC derived sebocytes represent a readily accessible and faithful in vitro model, which may also be relevant for the study of ethnic differences in skin lipid.

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References

Makrantonaki, E., Ganceviciene, R., & Zouboulis, C. (2011). An update on the role of the sebaceous gland in the pathogenesis of acne. Dermatoendocrinol, 3(1), 41-49. doi:10.4161/derm.3.1.13900

Pappas, A., Fantasia, J., & Chen, T. (2013). Age and ethnic variations in sebaceous lipids. Dermatoendocrinol, 5(2), 319-324. doi:10.4161/derm.25366

Xia, L., Zouboulis, C. C., & Ju, Q. (2009). Culture of human sebocytes in vitro. Dermatoendocrinol, 1(2), 92-95.