Skin pigmented using stem cells

August 23 2011

Having successfully reconstructed an epidermis using pluripotent stem cells in 2009 (1), Christine Baldeschi’s team at I-STEM (2) (I-STEM/Inserm UEVE U861/AFM), directed by Marc Peschanski, has just given it colour: using the same strategy, the researchers have obtained, in vitro, functional melanocytes, the cells that give skin its pigment and protect it from UV rays. This unlimited cell resource could, in time, be proposed as an alternative treatment for patients with skin pigmentation disorders, whether genetic in origin or not, such as Vitiligo. This research has been funded mainly thanks to donations to France’s Téléthon.

The results are published in PNAS and are available online

Figure 1: Cross section of human skin

One of the skin’s functions is to protect the body from the sun’s UV (ultraviolet) rays. This task is performed by pigment cells, called melanocytes. In releasing melanin, the pigment that colours the skin, they protect the other cells that form the epidermis, (keratinocytes) from the mutagenic effects of UV rays.

Cell therapy used to treat skin pigmentation disorders is currently performed by autografts. This strategy is only effective if there are unaffected areas adjacent to hypopigmented areas of skin, as is the case for Vitiligo, but not for many other pathologies, including albinism. To overcome this constraint, the researchers explored the possibilities of an alternative strategy based on an allogenic approach: to use an external and unlimited source of pigmented cells that can be totally controlled.

In 2009, the team succeeded for the first time in obtaining epidermis cells (keratinocytes) that enable constant renewal of the skin, derived from pluripotent embryonic stem cells. On the strength of the results published in The Lancet (November 2009), the team has now made a further breakthrough by identifying the differentiation process that enables them to derive human embryonic stem (hES) or induced pluripotent stem (iPS) cells, producing a pure and homogeneous population of melanocytes able to produce melanin and become integrated in the epidermis.

How are functional melanocytes derived from stem cells?

Pluripotent stem cells, whether embryonic (hES) or induced (iPS), have two fundamental characteristics: a capacity for unlimited growth and a capability of being pluripotent, in other words, of differentiating into every type of cell found in the human body.

Figure 2: a. Melanocyte culture (green) top); b. Melanocytes (green) cocultured with keratinocytes (red)

Dr Christine Baldeschi’s team identified the experimental conditions required for pluripotent cells to differentiate into pigmented cells (melanocytes) like those found naturally in the human epidermis. Once isolated and amplified in vitro, these cells present the same characteristics as adult melanocytes (cf. Figure 2.a).

With this culture, the researchers then studied how well the derived melanocytes functioned. They have demonstrated that they were both capable of engrafting into their niche in the basal layer of the epidermis (cf. Figure 1) and of communicating with the neighbouring keratinocytes, as happens physiologically in the epidermis. By analysing these cocultures, the research team discovered that these melanocytes can deliver their melanin to the keratinocytes that make up the epidermis (cf. Figure 2.b).

"This communication between cells is essential to protect the keratinocytes following stress caused by ultraviolet rays, and also to repigment the skin following a graft," explained Christine Baldeschi and Xavier Nissan.

The researchers believe that the prospects opened up by their study are far-reaching. "these ‘off the peg’ cells will be available to treat patients with Vitiligo as well as other pathologies that affect pigmentation and may be genetic, such as Waardenburg or Griscelli syndrome," said Marc Peschanski, Research Director at Inserm and Scientific Director of I-STEM.


Footnotes:
(1) 2009 : Première reconstitution d’un épiderme à partir de cellules souches embryonnaires humaines
(2) I-STEM: Institut des cellules souches pour le traitement et l'étude des maladies monogéniques - Institute for Stem cell Therapy and Exploration of Monogenic diseases, set up on 1 January 2005. The founding members are Inserm, Université d'Evry-Val-d'Essonne and the AFM.


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"Functional melanocytes derived from human pluripotent stem cells engraft into pluristratified epidermis"

Xavier NISSAN1, Lionel LARRIBERE1, Manoubia SAIDANI1, Ilse HURBAIN23, Cedric DELEVOYE23, Jessica FETEIRA45, Gilles LEMAITRE45, Marc PESCHANSKI45, Christine BALDESCHI45*

(1) CECS, I-Stem, AFM, 5 rue Henri Desbruères, 91030 Evry cedex, France,
(2) CNRS, UMR 144 Institut Curie, Centre de Recherche, Paris F-75248, France,
(3) Structure and Membrane Compartments, Cell and Tissue Imaging Facility (IBiSA)
(4) Inserm U-861, I-Stem, AFM, 91030 Evry cedex, France,
(5) UEVE U-861, I-Stem, AFM, 91030 Evry cedex, France

Proceedings of the National Academy of Sciences, 19 August 2011


Research contact

Xavier Nissan
I-Stem (I-Stem/Inserm/UEVE U861/AFM)
Tel.: +33 (0)1 69 90 85 91

Marc Peschanski
Research Director, Inserm
Scientific Director of I-STEM
Tel.: +33 (0)1 69 90 85 17

Press contacts

Juliette Hardy
Tel.: +33 (0)1 44 23 60 98

Anne-Sophie Midol, Stéphanie Bardon
Tel.: +33 (0)1 69 47 28 28

Djamila Hamed / Aude Escande
Tel.: +33 (0)1 69 47 80 71 or +33 (0)1 69 47 70 13

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