In vitro models of melanocytes : a brief literature review
Melanocyte are melanin producing cells that are responsible for the skin pigmentation, and its protection against UV irradiation (Mort et al., 2015). Human epidermal melanocytes for in vitro studies are mainly obtained from primary sources. However, in recent years, advancements in stem cell technology have led to the generation of melanocytes from human induced pluripotent stem cells (hiPSC-MEL) (Nissan et al., 2011). This brief review details how hiPSC-MEL compare to human epidermal melanocyte (HEM) in terms of morphology, marker expression and functions.
Similar to HEM, hiPSC-MEL display bipolar processes extending from a small ovoid body, with an overall elongated, spindle-like morphology (Nissan et al., 2011; Ohta et al., 2011). Electron microscopy of hiPSC-MEL revealed the presence of numerous pigmented melanosomes, representing all four stages of melanosome maturation (Nissan et al., 2011; Yang et al., 2011).
RNA and protein expression profile
hiPSC-MEL express many melanocyte specific markers at the RNA and protein levels such as the key transcription factor MITF (with a high level of the melanocyte specific isoform MITF-M), the SCF receptor c-Kit, S100 and MLANA. In addition, they express proteins of the melanin biosynthetic pathway such as PMEL17, DCT, TYRP1 and TYR. In addition, gene expression profile comparisons show that HEM and hiPSC-MEL are closely related (Jones et al., 2013; Ohta et al., 2011).
In vivo, melanocytes play a critical role in skin pigmentation in response to tanning agents such as sunlight mediated alpha-melanocyte-stimulating hormone (α-MSH) production (Schallreuter et al., 2008). Similarly to HEM, hiPSC-MEL are pigmented, and will increase their level of melanin production in response to α-MSH stimulation (Nissan et al., 2011).
Basal localization in 3D reconstructed skin model
In 3D reconstructed skin model where hiPSC-MEL are co-cultured with keratinocytes, they show correct localization in the basal layers of the epidermis (Jones et al., 2013; Mica et al., 2013; Nissan et al., 2011).
Melanosome transfer to keratinocytes
Once produced by melanocytes, melanin is transferred to the adjacent keratinocytes of the skin (Van Den Bossche et al., 2006). hiPSC-MEL are able to transfer melanosomes to keratinocytes in co-culture models (Nissan et al., 2011).
With the advances in hiPSC technology, it is now possible to produce hiPSC derived melanocytes that closely ressemble their primary counterparts in terms of morphology, marker expression and function. In addition, hiPSC-MEL represent a cost-effective alternative available in virtually unlimited quantity (from a single source).
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Jones, J.C., Sabatini, K., Liao, X., Tran, H.T., Lynch, C.L., Morey, R.E., Glenn-Pratola, V., Boscolo, F.S., Yang, Q., Parast, M.M., Liu, Y., Peterson, S.E., Laurent, L.C., Loring, J.F., Wang, Y.C., 2013. Melanocytes derived from transgene-free human induced pluripotent stem cells. J Invest Dermatol 133, 2104-2108.
Mica, Y., Lee, G., Chambers, S.M., Tomishima, M.J., Studer, L., 2013. Modeling neural crest induction, melanocyte specification, and disease-related pigmentation defects in hESCs and patient-specific iPSCs. Cell Rep 3, 1140-1152.
Mort, R.L., Jackson, I.J., Patton, E.E., 2015. The melanocyte lineage in development and disease. Development 142, 1387.
Nissan, X., Larribere, L., Saidani, M., Hurbain, I., Delevoye, C., Feteira, J., Lemaitre, G., Peschanski, M., Baldeschi, C., 2011. Functional melanocytes derived from human pluripotent stem cells engraft into pluristratified epidermis. Proc Natl Acad Sci U S A 108, 14861-14866.
Ohta, S., Imaizumi, Y., Okada, Y., Akamatsu, W., Kuwahara, R., Ohyama, M., Amagai, M., Matsuzaki, Y., Yamanaka, S., Okano, H., Kawakami, Y., 2011. Generation of human melanocytes from induced pluripotent stem cells. PLoS One 6, e16182.
Schallreuter, K.U., Kothari, S., Chavan, B., Spencer, J.D., 2008. Regulation of melanogenesis--controversies and new concepts. Exp Dermatol 17, 395-404.
Van Den Bossche, K., Naeyaert, J.M., Lambert, J., 2006. The quest for the mechanism of melanin transfer. Traffic 7, 769-778.
Yang, R., Jiang, M., Kumar, S.M., Xu, T., Wang, F., Xiang, L., Xu, X., 2011. Generation of melanocytes from induced pluripotent stem cells. J Invest Dermatol 131, 2458-2466.