We report on a functional human model to evaluate multi-organ toxicity in a 4-organ system under continuous flow conditions in a serum-free defined medium utilizing a pumpless platform for 14 days. Computer simulations of the platform established flow rates and resultant shear stress within accepted ranges. Viability of the system was demonstrated for 14 days as well as functional activity of cardiac, muscle, neuronal and liver modules. The pharmacological relevance of the integrated modules were evaluated for their response at 7 days to 5 drugs with known side effects after a 48 hour drug treatment regime. The results of all drug treatments were in general agreement with published toxicity results from human and animal data. The presented phenotypic culture model exhibits a multi-organ toxicity response, representing the next generation of in vitro systems, and constitutes a step towards an in vitro “human-on-a-chip” assay for systemic toxicity screening.

Epidermal T cells have been shown to play unique roles in tissue homeostasis and repair in mice through local secretion of distinct growth factors in the skin. Human epidermis contains both αβ+ and γδ+ T cells whose functional capabilities are not understood. We demonstrate that human epidermal T cells are able to produce insulin-like growth factor 1 (IGF-1) upon activation and promote wound healing in a skin organ culture model. Moreover, an analysis of the functional capabilities of T cells isolated from acute versus chronic wounds revealed a striking difference. Both αβ+ and Vδ1+ T cells isolated from acute wounds actively produced IGF-1, demonstrating that they are activated during tissue damage to participate in wound repair. In contrast, IGF-1 production could not be detected in T cells isolated from chronic wounds. In fact, skin T cells isolated from chronic wounds were refractory to further stimulation, suggesting an unresponsive state. Collectively, these results define a novel role for human epidermis–resident T cells in wound healing and provide new insight into our understanding of chronic wound persistence.

Skin aging is associated with changes in cutaneous physiology including interactions with a skin microbial community. A striking alteration and diversification in the skin microbiome with aging was observed between two different age groups of 37 healthy Japanese women, i.e. younger adults of 21–37 years old and older adults of 60–76 years old, using bacterial 16S rRNA gene sequencing. The analyses revealed that the alpha diversity/species richness was significantly higher in the older than the younger group for the cheek and forehead microbiomes, while the beta diversity in the overall structure significantly differed particularly for the forearm and scalp microbiomes between the two age groups. Taxonomic profiling showed a striking reduction in the relative abundance of the majority skin genus Propionibacterium in the cheek, forearm and forehead microbiomes of the older adults, and identified 38 species including many oral bacteria that significantly differentiated the two age groups with a skin site dependency. Furthermore, we found chronological age-related and unrelated skin clinical parameters that correlate with the observed changes in the skin microbiome diversity. Thus, our data suggested that the diversification of skin microbiomes in adult women was largely affected by chronological and physiological skin aging in association with oral bacteria.

The bacterial and fungal communities associated with dandruff were investigated using culture-independent methodologies in the French subjects. The major bacterial and fungal species inhabiting the scalp subject’s were identified by cloning and sequencing of the conserved ribosomal unit regions (16S for bacterial and 28S-ITS for fungal) and were further quantified by quantitative PCR. The two main bacterial species found on the scalp surface were Propionibacterium acnes and Staphylococcus epidermidis, while Malassezia restricta was the main fungal inhabitant. Dandruff was correlated with a higher incidence of M. restricta and S. epidermidis and a lower incidence of P. acnes compared to the control population (p<0.05). These results suggested for the first time using molecular methods, that dandruff is linked to the balance between bacteria and fungi of the host scalp surface.

V. filiformis lysate significantly improved AD. This may be in part due to reduction of S. aureus, but seems to relate in most parts to a direct immunomodulatory effect on skin-associated immune responses.