Bioengineering and in utero transplantation of fetal skin in the sheep model: A crucial step towards clinical application in human fetal spina bifida repair

An intricate problem during open human fetal surgery for spina bifida regards back skin closure, particularly in those cases where the skin defect is much too large for primary closure. We hypothesize that tissue engineering of fetal skin might provide an adequate autologous skin substitute for in utero application in such situations. Eight sheep fetuses of four time-mated ewes underwent fetoscopic skin biopsy at 65 days of gestation. Fibroblasts and keratinocytes isolated from the biopsy were used to create fetal dermo-epidermal skin substitutes. These were transplanted on the fetuses by open fetal surgery at 90 days of gestation on skin defects (excisional wounds) created during the same procedure. Pregnancy was allowed to continue until euthanasia at 120 days of gestation. The graft area was analyzed macroscopically and microscopically. The transplanted fetal dermo-epidermal skin substitutes was well discernable in situ in three of the four fetuses available for analysis. Histology confirmed healed grafts with a close to natural histological skin architecture four weeks after in utero transplantation. This experimental study generates evidence that laboratory grown autologous fetal skin analogues can successfully be transplanted in utero. These results have clinical implications as an analogous procedure might be applied in human fetuses undergoing prenatal repair to facilitate primary skin closure. Finally, this study may also fertilize the field of fetal tissue engineering in general, particularly when more interventional, minimally invasive, and open fetal surgical procedures become available

Systematic Literature Review: Ability of the IBDQ-32 to Detect Meaningful Change in Ulcerative Colitis Health Indicators

Purpose: Previous reviews produced weak evidence regarding the responsiveness of the Inflammatory Bowel Disease Questionnaire (IBDQ-32) to changes in ulcerative colitis (UC) health indicators. This systematic review and meta-analysis provide an updated synthesis on IBDQ-32 responsiveness. Methods: A systematic literature review identified 11 articles reporting IBDQ-32 responder analyses in randomized control trials, which were included in a random effects meta-analysis, and 15 articles linking IBDQ-32 change to change in UC health indicators, which were summarized narratively. Meta-analysis compared differences between IBDQ-32 responder proportions in efficacious and nonefficacious treatment arms relative to placebo. Linear meta-regression examined the association of treatment efficacy and proportions of IBDQ-32 responders in active treatment compared with placebo. Results: Meta-analysis showed larger differences in IBDQ-32 response proportions between active treatment and placebo for efficacious treatments (pooled OR, 2.19; 95% CI, 1.83-2.63) than nonefficacious treatments (pooled OR, 1.21; 95% CI, 0.84-1.74; Cochran's Q[df = 1] = 8.26, P = .004). Meta-regression showed that the magnitude of treatment efficacy positively predicted IBDQ-32 response in active treatments relative to placebo (β = 0.21, P < .001). Moderate to strong correlations were found between change in IBDQ-32 and change in health indicators (eg, patient-reported measures, disease activity, endoscopic indices; correlations, 0.37-0.64 in absolute values). Patients achieving clinical response or remission showed greater change in IBDQ-32 total scores (range, 22.3-50.1 points) and more frequently met clinically meaningful thresholds on the IBDQ-32 than those not achieving clinical response or remission (all P < .05). Conclusions: The IBDQ-32 is responsive to changes in UC health indicators and disease activity, including in response to efficacious treatment (relative to placebo)

Characterization of Distinct Chondrogenic Cell Populations of Patients Suffering from Microtia Using Single-Cell Micro-Raman Spectroscopy

Microtia is a congenital condition of abnormal development of the outer ear. Tissue engineering of the ear is an alternative treatment option for microtia patients. However, for this approach, the identification of high regenerative cartilage progenitor cells is of vital importance. Raman analysis provides a novel, non-invasive, label-free diagnostic tool to detect distinctive biochemical features of single cells or tissues. Using micro-Raman spectroscopy, we were able to distinguish and characterize the particular molecular fingerprints of differentiated chondrocytes and perichondrocytes and their respective progenitors isolated from healthy individuals and microtia patients. We found that microtia chondrocytes exhibited lower lipid concentrations in comparison to healthy cells, thus indicating the importance of fat storage. Moreover, we suggest that collagen is a useful biomarker for distinguishing between populations obtained from the cartilage and perichondrium because of the higher spectral contributions of collagen in the chondrocytes compared to perichondrocytes from healthy individuals and microtia patients. Our results represent a contribution to the identification of cell markers that may allow the selection of specific cell populations for cartilage tissue engineering. Moreover, the observed differences between microtia and healthy cells are essential for gaining better knowledge of the cause of microtia. It can be useful for designing novel treatment options based on further investigations of the discovered biochemical substrate alterations

CXCR6 and its ligand CXCL16 preferentially mediate CD8+ T cell recruitment into psoriatic skin

Psoriatic skin lesions are characterized by an inflammatory cellular infiltrate, which is recruited by a defined set of chemokines. The most dominant infiltrating cell types are monocytes, CD4+ and CD8+ T cells. Chemokines governing CD4+ T cell recruitment into psoriatic skin are well characterized and include CCR4, CCR6, CCR10, and CXCR3 ligands. In contrast, chemokine-chemokine receptors pairs that regulate recruitment of CD8+ T cells are less well understood. To this end, we studied chemokine receptors on peripheral blood T cells and monocytes and identified CXCR6 as a dominant chemokine receptor on monocytes and CD8+ but not on CD4+ T cells of psoriatic patients. Moreover, CXCR6 mRNA expression was more pronounced in CD8+ T cells from psoriatic skin compared to CD8+ T cells from blood of psoriatic patients and expression levels were higher than for any other chemokine receptor analyzed. Next, CXCR6 and its ligand CXCL16 were analyzed in psoriatic skin by immunofluorescence. CXCL16 was mainly found on cutaneous monocytes, keratinocytes, and dendritic cells and its receptor CXCR6 on T cells and monocytes. Functional consequences were analyzed demonstrating CXCL16 induced Ca2+ influx and migration of skin derived CD8+ T cells in vitro. In vivo, CXCL16 most potently recruited blood derived CD8+ T cells to human skin grafts previously transplanted onto SCID-mice. These investigations indicate that CXCL16 and CXCR6 represent an important ligand-receptor pair mediating CD8+ T cell recruitment in to psoriatic skin

Ge coordination in NaAlG e 3 O 8 glass upon compression to 131 GPa

International audienceStructural transformations at high pressure in NaAlGe3O8 glass were investigated by means of x-ray absorption spectroscopy at the Ge K edge in combination with a diamond anvil cell. The obtained results provide a detailed picture of the local structural behavior of Ge in a chemically complex glass under compression. First and second shell bond distances (RGe-O and RGe...Ge) were extracted assuming contributions of two scattering paths (Ge-O and Ge…Ge). We observed a significant extension of the Ge-O distance from 1.73 to 1.82 Å between 3 and ∼26GPa, accompanied by an increase of the fitted number of nearest neighbors from ∼4 to ∼6. These observations can be attributed to the change from tetrahedral to octahedral Ge coordination. Second shell bond distances Ge…Ge are also consistent with this structural transformation. Between 34 and 131 GPa, the evolution of the fitted Ge-O distance implies a gradual volume reduction of the Ge octahedra. At the highest probed pressure of 131 GPa a Ge-O distance of 1.73 Å was found, which is similar to the one obtained at ambient conditions for Ge in fourfold coordination. The compressibility of the Ge-O octahedron in NaAlGe3O8 beyond 34 GPa is considerably higher than the one reported for amorphous GeO2 from x-ray diffraction analysis but it is similar to the one reported for the Ge octahedron in crystalline rutile-type GeO2. We attribute the high compressibility of the Ge-O bond in NaAlGe3O8 glass to the presence of Al and Na that increase the system's complexity and therefore its degrees of freedom. Beyond 110 GPa the data on NaAlGe3O8 glass indicate the onset of polyhedral distortion. The performed study provides insights into the structural changes of complex and polymerized germanate glasses or melts at extreme pressure conditions

A highly porous flexible metal–organic framework with corundum topology

A flexible Metal–Organic Framework Zn4O(BenzTB)3/2 (DUT-13) was obtained by combination of a tetratopic linker and Zn4O6+ as connector. The material has a corundum topology and shows the highest pore volume among flexible MOFs