Impact of microstructure on cell behavior and tissue mechanics in collagen and dermal decellularized extra-cellular matrices.

Skin models are used for many applications such as research and development or grafting. Unfortunately, most lack a proper microenvironment producing poor mechanical properties and inaccurate extra-cellular matrix composition and organization. In this report we focused on mechanical properties, extra-cellular matrix organization and cell interactions in human skin samples reconstructed with pure collagen or dermal decellularized extra-cellular matrices (S-dECM) and compared them to native human skin.

A perfusable vascularized full-thickness skin model for potential topical and systemic applications.

Vascularization of reconstructed tissues is one of the remaining hurdles to be considered to improve both the functionality and viability of skin grafts and the relevance ofapplications. Our study, therefore, sought to develop a perfusable vascularized full-thickness skin equivalent that comprises a more complex blood vasculature compared to existing models. We combined molding, auto-assembly and microfluidics techniques in order to create a vascularized skin equivalent representing (a) a differentiated epidermis with a physiological organization and correctly expressing K14, K10, Involucrin, TGM1 and Filaggrin, (b) three perfusable vascular channels with angiogenic sprouts stained with VE-Caderin and Collagen IV, (c) an adjacent microvascular network created via vasculogenesis and connected to the sprouting macrovessels.

Utilization of patterned bioprinting for heterogeneous and physiologically representative reconstructed epidermal skin models.

Organotypic skin tissue models have decades of use for basic research applications, the treatment of burns, and for efficacy/safety evaluation studies. The complex and heterogeneous nature of native human skin however creates difficulties for the construction of physiologically comparable organotypic models. Within the present study, we utilized bioprinting technology for the controlled deposition of separate keratinocyte subpopulations to create a reconstructed epidermis with two distinct halves in a single insert, each comprised of a different keratinocyte sub-population, in order to better model heterogonous skin and reduce inter-sample variability.

Senescence-associated SIN3B promotes inflammation and pancreatic cancer progression.

Pancreatic ductal adenocarcinoma (PDAC) is strikingly resistant to conventional therapeutic approaches. We previously demonstrated that the histone deacetylase-associated protein SIN3B is essential for oncogene-induced senescence in cultured cells. Here, using a mouse model of pancreatic cancer, we have demonstrated that SIN3B is required for activated KRAS-induced senescence in vivo.

Regulation and function of FoxO transcription factors in normal and cancer stem cells: what have we learned?

Forkhead FoxO transcription factors exert critical biological functions in response to genotoxic stress. In mammals four FoxOs proteins are known. FoxOs induce cell cycle arrest, repair damaged DNA, or initiate apoptosis by modulating genes that control these processes.

Early alteration of the self-renewal/differentiation threshold in trophoblast stem cells derived from mouse embryos after nuclear transfer.

Development after nuclear transfer (NT) is subjected to defects originating from both the epiblast and the trophoblast parts of the conceptus and is always accompanied by placentomegaly at term. Here we have investigated the origin of the reprogramming errors affecting the trophoblast lineage in mouse NT embryos. We show that trophoblast stem (TS) cells can be derived from NT embryos (ntTS cells) and used as an experimental in vitro model of trophoblast proliferation and differentiation.

Trophoblast stem cell derivation, cross-species comparison and use of nuclear transfer: new tools to study trophoblast growth and differentiation.

The trophoblast is a supportive tissue in mammals that plays key roles in embryonic patterning, foetal growth and nutrition. It shows an extensive growth up to the formation of the placenta. This growth is believed to be fed by trophoblast stem cells able to self-renew and to give rise to the differentiated derivatives present in the placenta.