Skin models and hiPSC: toward a new paradigm
The skin is the largest organ of the human body: it plays a key protective role, as well as an important social role. The skin consists of two superposed layers, the epidermis and the dermis. Keratinocytes form the epidermal barrier, while subjacent melanocytes are responsible for its pigmentation. The underlying dermal compartment is mostly made of fibroblasts. It also contains hair follicle s, blood vessels, and a variety of glands including sebaceous glands (responsible for sebum production).Up until recently, in vitro dermo-cosmetic research carried out to evaluate ingredient toxicity/efficacy relied on immortalized cell lines, or primary cell sources. While immortalized cell lines grow indefinitely, they often carry abnormal karyotypes, and may not fully resume the expected phenotype. On the other hand, primary cells obtained from skin biopsies can be difficult to isolate and expand.
The thriving technology of induced pluripotent stem cells (hiPSC) has spread to many fields of in vitro cell research over the last decade (Omole & Fakoya, 2018). Induced pluripotent stem cells are obtained following the epigenetic reprogramming of somatic cells by the forced expression of a set of well-defined transcription factors. While reprogramming was historically achieved using integrating lentiviruses, non-integrative approaches have been developed since then, based on mRNA, protein, or episomes. At Phenocell, blood cells and fibroblasts are routinely reprogrammed into hiPSC using footprint free episomal vectors.
Like other stem cells, hiPSC have the potential to self-renew indefinitely. However, what sets them apart is their pluripotency, that is, the ability to differentiate into any cell of the human body. Therefore, hiPSC potentially represent an unlimited source of somatic cells, such as skin cells (Guo et al., 2013).
Over the years, Phenocell has developed robust protocols for the large-scale production of skin cells from hiPSC: keratinocytes, melanocytes and sebocytes are now available in large quantities, while fibroblasts are being actively pursued. Additionally, sourcing specific donors needs only to be performed once with hiPSC technology, as they afterwards become available in virtually unlimited supply. To this end, Phenocell has assembled a cohort of healthy ethnic donors of Caucasian, Asian and African origin, while actively sourcing rare disease donors.
In conclusion, thanks to hiPSC technology it is now possible to obtain large quantities of skin cells of unmatched quality, from selected donors. This feat opens the door to the development of ethnic specific skin care, or personalized medicine.
Guo, Z., Higgins, C. A., Gillette, B. M., Itoh, M., Umegaki, N., Gledhill, K., . . . Christiano, A. M. (2013). Building a microphysiological skin model from induced pluripotent stem cells. Stem Cell Res Ther, 4 Suppl 1, S2. doi:10.1186/scrt363
Omole, A. E., & Fakoya, A. O. J. (2018). Ten years of progress and promise of induced pluripotent stem cells: historical origins, characteristics, mechanisms, limitations, and potential applications. PeerJ, 6, e4370. doi:10.7717/peerj.4370