Gilles Lemaître : Research engineer (Evry University), bound to the Genodermatoses team
The human Embryonic Stem Cells and cell therapy
Thanks to their capacity for self-renewal and pluripotency, the human Embryonic Stem Cells (hESCs) represent an unlimited source of cells that can theoretically be differentiated in all cell types of the body. The reconstruction of epidermis from keratinocytes derived from hESCs would therefore represent a therapeutic option for patients with allografts of some genodermatosis. Moreover, the expression of HLA antigens is low and would limit the immune response of the host against the graft and thereby prevent rejection in transplants.
In the last 5 years several international teams have tried to differentiate hESCs into cells with a phenotype similar to that of keratinocytes. This work, initially promising, have not resulted in the generation of a functional epidermis.
Our team is meeting this challenge by publishing a protocol of sequential differentiation to derive hESC into a pure and homogeneous population of keratinocytes capable of reconstituting a multilayered epidermis both in vitro and
in vivo.
Of human embryonic stem cells in the epidermis ...
The main result of our study is to establish a protocol to differentiate hESC into functional keratinocytes. The commitment of hESC in the epidermal lineage was made possible by combining both a co-culture of feeder cells and pharmacological treatment over 40 days. Cells acquire a phenotype of epithelial cells just before making a final commitment in the keratinocyte lineage.
The functionality of these cells has been demonstrated through their ability to generate a multilayered epidermis in vitro with all layers of human skin.
In order to implement this model for cell therapy we also conducted studies of transplantation in vivo in mice. Twelve weeks after transplantation, in these conditions of homeostasis, the graft presents a pluristratified architecture similar to adult skin. Moreover, the reconstructed epidermis from keratinocytes derived from hESCs maintain a low level of expression of markers HLA DR and ABC making them suitable for cell therapy.
... A new step towards treating genodermatosis
The results of this study demonstrate that we have obtained an inexhaustible source of keratinocytes weakly immunogenic capable of forming a skin that can be grafted. The team "cell therapy for genodermatosis" intends to establish protocols of pluripotent cells differentiation such as hESC or iPS putting themselves in GMP conditions (clinical grade) to open a therapeutic approach in treating genodermatosis.
