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Human 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 consist in a secretory compartment composed of berry-like structures, the acini, connected to a common excretory duct. Sebum, the product of sebocyte activity, is 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 effects on skin and face, acne can profoundly impact the 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.


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. Primary cultures of human sebocytes were progressively established, but the technique is challenging and yields limited amount of cells. 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 display abnormal karyotypes.

     Phenocell has developed innovative protocols for the production of sebocytes from human induced pluripotent stem cells (iPSC). iPSC-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, iPSC-derived sebocytes of African origin produce significantly more lipid than their Caucasian and Asian counterparts (Figure 2). These results are in line with in vivo data that show 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 has been limited by lack of cellular models available in large quantities and that display complete functional properties.

iPSC derived sebocytes represent a readily accessible and faithful in vitro model, which may also be relevant for the study of ethnic differences in skin physiology.

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.

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