Neural crest–derived cells with stem cell features can be traced back to multiple lineages in the adult skin

Given their accessibility, multipotent skin-derived cells might be useful for future cell replacement therapies. We describe the isolation of multipotent stem cell–like cells from the adult trunk skin of mice and humans that express the neural crest stem cell markers p75 and Sox10 and display extensive self-renewal capacity in sphere cultures. To determine the origin of these cells, we genetically mapped the fate of neural crest cells in face and trunk skin of mouse. In whisker follicles of the face, many mesenchymal structures are neural crest derived and appear to contain cells with sphere-forming potential. In the trunk skin, however, sphere-forming neural crest–derived cells are restricted to the glial and melanocyte lineages. Thus, self-renewing cells in the adult skin can be obtained from several neural crest derivatives, and these are of distinct nature in face and trunk skin. These findings are relevant for the design of therapeutic strategies because the potential of stem and progenitor cells in vivo likely depends on their nature and origin

A single epidermal stem cell strategy for safe ex vivo gene therapy.

There is a widespread agreement from patient and professional organisations alike that the safety of stem cell therapeutics is of paramount importance, particularly for ex vivo autologous gene therapy. Yet current technology makes it difficult to thoroughly evaluate the behaviour of genetically corrected stem cells before they are transplanted. To address this, we have developed a strategy that permits transplantation of a clonal population of genetically corrected autologous stem cells that meet stringent selection criteria and the principle of precaution. As a proof of concept, we have stably transduced epidermal stem cells (holoclones) obtained from a patient suffering from recessive dystrophic epidermolysis bullosa. Holoclones were infected with self-inactivating retroviruses bearing a COL7A1 cDNA and cloned before the progeny of individual stem cells were characterised using a number of criteria. Clonal analysis revealed a great deal of heterogeneity among transduced stem cells in their capacity to produce functional type VII collagen (COLVII). Selected transduced stem cells transplanted onto immunodeficient mice regenerated a non-blistering epidermis for months and produced a functional COLVII. Safety was assessed by determining the sites of proviral integration, rearrangements and hit genes and by whole-genome sequencing. The progeny of the selected stem cells also had a diploid karyotype, was not tumorigenic and did not disseminate after long-term transplantation onto immunodeficient mice. In conclusion, a clonal strategy is a powerful and efficient means of by-passing the heterogeneity of a transduced stem cell population. It guarantees a safe and homogenous medicinal product, fulfilling the principle of precaution and the requirements of regulatory affairs. Furthermore, a clonal strategy makes it possible to envision exciting gene-editing technologies like zinc finger nucleases, TALENs and homologous recombination for next-generation gene therapy

Les effets de l’EEE sur le développement professionnel des enseignants et l’expérience d’apprentissage des étudiants : Comparaison de deux cas suisses

En suisse, les institutions d’enseignement supérieur disposent d’une autonomie importante pour implémenter leur modèle d’évaluation des enseignements par les étudiants (EEE). Certaines, comme l’Université de Lausanne, ont opté pour des modèles minimisant la part de contrôle ; d’autres, comme la Haute école d'ingénierie et de gestion du Canton de Vaud, ont préféré contrôler davantage la prestation enseignante. L’espace suisse de l’enseignement supérieur constitue donc un terrain de recherche intéressant pour s’interroger sur les impacts de l’EEE. Dans le présent travail, les auteurs ont opté pour une étude de cas mobilisant des données quantitatives et qualitatives afin de chercher à comprendre si l’impact sur le développement professionnel des enseignants et l’expérience d’apprentissage des étudiants diffère selon le modèle d’EEE utilisé. sur la base des résultats, les auteurs débattront du développement professionnel des enseignants et de l’expérience d’apprentissage des étudiants en lien avec l’EEE, puis concluront avec quelques perspectives de recherches futures.In switzerland, higher education institutions have a high level of independance regarding the implementation of evaluation of teaching by students. some institutions such as the University of Lausanne have opted for models keeping control to a minimum ; other institutions, such as the yverdon school of Engineering and Business, have chosen to put in place a system that aims at controlling the performance of teachers. swiss higher education institutions offer an interesting ground for research into the impact of teaching evaluation policies. In this paper, the authors chose a mixed qualitative and quantitative case study approach in order to examine the impact of different students ratings processes on fostering the professional development of teachers and the learning experience of students. They conclude the paper with suggestions for further research.Avaliação dos professores pelos estudantes (APE). Algumas, como a Universidade de Lausanne, optaram por modelos que minimizam a parte do controlo ; outras, como a Escola superior de Gestão do Cantão de Vaud, preferiram, pelo contrário, controlar a prestação do professor. O espaço suíço do ensino superior constitui, assim, um terreno interessante de investigação para se interrogar a APE. No presente trabalho, os autores optaram por um estudo de caso, mobilizando dados quantitativos e qualitativos, no sentido de procurar compreender se o impacto sobre o desenvolvimento profissional dos professores e a experiência de aprendizagem dos estudantes difere segundo o modelo de APE utilizado. A partir dos resultados, os autores debaterão o desenvolvimento profissional dos professores e a experiência de aprendizagem dos estudantes em ligação com a APE, concluindo com a apresentação de algumas perspetivas de investigações futuras

Location of corneal epithelial stem cells Reply

The longstanding concept that corneal epithelial stem cells reside mainly in the limbus is supported by the absence of major corneal epithelial differentiation markers, that is, K3 and K12 keratins, in limbal basal cells (these markers are expressed, however, in corneal basal cells, thus distinguishing the mode of keratin expression in corneal epithelium from that of all other stratified epithelia), the centripetal migration of corneal epithelial cells, the exclusive location of slow-cycling cells in the limbal basal layer, the superior in vitro proliferative potential of limbal epithelial cells, and the transplanted limbal cells' ability to reconstitute corneal epithelium in vivo (reviewed in refs 1-4). Moreover, previous data indicate that corneal and conjunctival epithelia represent two separate cell lineages (reviewed in refs 1-4). Majo et al. suggested, however, that corneal and conjunctival epithelia are equipotent, and that identical oligopotent stem cells are present throughout the corneal, limbal and conjunctival epithelia. We point out here that these suggestions are inconsistent with many known growth, differentiation and cell migration properties of the anterior ocular epithelia

Tp63-expressing adult epithelial stem cells cross lineages boundaries revealing latent hairy skin competence

The formation of hair follicles, a landmark of mammals, requires complex mesenchymal–epithelial interactions and it is commonly believed that embryonic epidermal cells are the only cells that can respond to hair follicle morphogenetic signals in vivo. Here, we demonstrate that epithelial stem cells of non-skin origin (e.g. that of cornea, oesophagus, vagina, bladder, prostate) that express the transcription factor Tp63, a master gene for the development of epidermis and its appendages, can respond to skin morphogenetic signals. When exposed to a newborn skin microenvironment, these cells express hair-follicle lineage markers and contribute to hair follicles, sebaceous glands and/or epidermis renewal. Our results demonstrate that lineage restriction is not immutable and support the notion that all Tp63-expressing epithelial stem cells, independently of their embryonic origin, have latent skin competence explaining why aberrant hair follicles or sebaceous glands are sometimes observed in non-skin tissues (e.g. in cornea, vagina or thymus)

Pore Size Manipulation in 3D Printed Cryogels Enables Selective Cell Seeding

Cryogels are macroporous materials that display remarkable properties, such as high pore interconnection, large surface to volume ratio, and high mechanical stability, making them good candidates for 3D cell culture. However, shaping cryogels remains challenging because of the harsh conditions of synthesis at temperatures as low as −80 °C. In this paper, a solution for the 3D printing of functionalized cryogels is proposed. A microfabricated dispensing probe allowing the last second mixing of cryogel precursors as well as control of the temperature of the extruded material during printing is presented. This dispensing tool allows multilayer 3D printing of cryogels with on demand local pore size change through the control in temperature of the dispensed solution. Moreover, thanks to advanced functionalization of the scaffold, cells can be cultured in 3D within the printed scaffold and exhibited spreading. The ability to tune the pore size of the printed cryogels allows to select during printing where cells will get seeded