Functional disruption of cortical cingulate activity attenuates visceral hypersensitivity and anxiety induced by acute experimental colitis.

Visceral pain is a highly complex experience and is the most common pathological feature in patients suffering from inflammatory gastrointestinal disorders. Whilst it is increasingly recognized that aberrant neural processing within the gut-brain axis plays a key role in development of neurological symptoms, the underlying mechanisms remain largely unknown. Here, we investigated the cortical activation patterns and effects of non-invasive chemogenetic suppression of cortical activity on visceral hypersensitivity and anxiety-related phenotypes in a well-characterized mouse model of acute colitis induced by dextran sulfate sodium (DSS). We found that within the widespread cortical network, the mid-cingulate cortex (MCC) was consistently highly activated in response to innocuous and noxious mechanical stimulation of the colon. Furthermore, during acute experimental colitis, impairing the activity of the MCC successfully alleviated visceral hypersensitivity, anxiety-like behaviors and visceromotor responses to colorectal distensions (CRDs) via downregulating the excitability of the posterior insula (PI), somatosensory and the rostral anterior cingulate cortices (rACC), but not the prefrontal or anterior insula cortices. These results provide a mechanistic insight into the central cortical circuits underlying painful visceral manifestations and implicate MCC plasticity as a putative target in cingulate-mediated therapies for bowel disorders.

A Thymic Epithelial Stem Cell Pool Persists throughout Ontogeny and Is Modulated by TGF-ß.

Adult tissue-specific stem cells (SCs) mediate tissue homeostasis and regeneration and can give rise to all lineages in the corresponding tissue, similar to the early progenitors that generate organs in the first place. However, the developmental origins of adult SCs are largely unknown. We recently identified thymosphere-forming stem cells (TSFCs) in the adult mouse thymus, which display genuine stemness features and can generate the two major thymic epithelial cell lineages. Here, we show that embryonic TSFCs possess stemness features but differ from adult TSFCs in surface marker profile. Our findings support the model of a continuous thymic SC lineage that is maintained throughout ontogeny. TGF-ß signaling differentially affects embryonic versus adult thymosphere formation, suggesting that thymic epithelial SC potency depends on both developmental stage and environmental signals. Collectively, our findings suggest that embryonic TSFCs contribute to an adult SC pool and that TSFC plasticity is controlled by TGF-ß signaling.

Influence of Duration and Temperature of Transport and Storage Prior to Processing on Cell Quality of Cord Blood Units--A German. Experience.

BACKGROUND: In Germany, cord blood needs to be transported to the processing facility to be processed and cryopreserved within 48 hours after collection according to national guidelines. During that time, a temperature of 22 ± 4 degrees C must be maintained. The purpose of this study was to analyse the influence of temperature during transport and storage prior to processing and cryopreservation on stem cells in 2460 both autologous and allogeneic umbilical cord blood samples. METHODS: Total and viable CD45+ cells, total and viable CD34+ cells, and mononuclear cells (MNC) of cord blood and resulting leucocyte concentrate both before and after freezing were analysed by flow cytometry. Transport protocols and the records of temperature measuring chips used in transport were evaluated in order to analyse how long each unit was exposed to which temperature ranges. RESULTS: On average, the cord blood preparations were delivered within 16.4 ± 6.3 hours. No cord blood was delivered and processed later than 48 hours after donation. Temperature of transport and storage before processing had minor but sometimes significant effects on cell viability. A temperature range of 20 - 24 degrees C showed best survival rates for CD34+ cells and highest colony forming potential. CONCLUSIONS: The temperature prior to processing has little yet sometimes significant effects on cell viability in stem cell concentrates prepared from cord blood. However, the absolute differences in cell viabilities are quite small. Therefore, the effect is clinically negligible in a range from 4 degrees C to 28 degrees C if cryopreservation is done within 48 hours.