Gilles Lemaitre

The skin provides a model for regenerative medicine, prompting the design of cultured reconstructed tissue substitutes. Translational research and bioengineering have indeed given rise to clinical applications such as the grafting of cultured skin substitutes in severe burn patients, more than four decades ago, and more recently the correction of a genodermatosis by a cell and gene therapy approach. In addition, therapeutic uses of bioengineered skin substitutes are considered for chronic wounds and ulcers, which affect much larger patient populations. This history has given rise to multiple innovations involving original concepts, combined with new methodological and technical approaches. The variables relate to the cell sources used, which may include cells from neonatal or adult skin, autologous or allogeneic, or skin cells obtained by directed differentiation of pluripotent stem cells. They also concern methods and culture protocols used for cell expansion phase in two‐dimensional (2D) culture, then the production phase of 3D skin substitutes, a major current challenge being the elimination of constituents not chemically defined and/or of animal origin. By outlining the main technological options, this review aims to guide the design of next‐generation skin substitutes that will reconcile biological performance, regulatory expectations and realistic clinical implementation.

The epidermis hosts populations of epithelial stem cells endowed with well-documented renewal and regenerative functions. This tissue thus constitutes a model for exploring the molecular characteristics of stem cells, which remain to date partially characterized at the molecular level in human skin. Our group has investigated the regulatory functions of the KLF4/TGFB1 and the MAD4/MAX/MYC signaling pathways in the control of the immaturity-stemness versus differentiation fate of keratinocyte stem and precursor cells from human interfollicular epidermis. We described that down-modulation of either KLF4 or MXD4/MAD4 using RNA interference tools promoted an augmented stemness cellular status; an effect which was associated with significant transcriptional changes, as assessed by RNA-sequencing. Here, we have implemented a computational approach aimed at integrating the level of the coding genome, comprising the transcripts encoding conventional proteins, and the non-coding genome, with a focus on long non-coding RNAs (lncRNAs). In addition, datasets of micro-RNAs (miRNAs) with validated functions were interrogated in view of identifying miRNAs that could make the link between protein-coding and non-coding transcripts. Putative regulons comprising both coding and long non-coding transcripts were built, which are expected to contain original pro-stemness candidate effectors available for functional validation approaches. In summary, interpretation of our basic functional data together with in silico biomodeling gave rise to a prospective picture of the complex constellation of transcripts regulating the keratinocyte stemness status.

Melanocytes are essential for skin homeostasis and protection, and their loss or misfunction leads to a wide spectrum of diseases. Cell therapy utilizing autologous melanocytes has been used for years as an adjunct treatment for hypopigmentary disorders such as vitiligo. However, these approaches are hindered by the poor proliferative capacity of melanocytes obtained from skin biopsies. Recent advances in the field of human pluripotent stem cells have fueled the prospect of generating melanocytes. Here, we have developed a well-characterized method to produce a pure and homogenous population of functional and proliferative melanocytes. The genetic stability and potential transformation of melanocytes from pluripotent stem cells have been evaluated over time during the in vitro culture process. Thanks to transcriptomic analysis, the molecular signatures all along the differentiation protocol have been characterized, providing a solid basis for standardizing the protocol. Altogether, our results promise meaningful, broadly applicable, and longer-lasting advances for pigmentation disorders and open perspectives for innovative biotherapies for pigment disorders.

Over the last decade, various protocols have been published to generate melanocytes from human pluripotent stem cells (CSP). However, there is li | POSTER

Chronic wounds, such as leg ulcers associated with sickle cell disease, occur as consequence of a prolonged inflammatory phase during the healing | POSTER

Epidermolysis Bullosa Simplex (EBS), an autosomal dominant skin disorder, is characterized by skin fragility. Genetically, majority of cases are | POSTER