Objective To show the responsiveness of a tissue engineered human endometrial stroma to combinations of hormones mimicking the secretory and menstrual phases of the cycle. Design In vitro experimental study Setting University uterine biology research laboratory Cells Telomerase immortalized human endometrial stromal cells Interventions The stromal cells were cultured in monolayers (2D) or encapsulated in a collagen I hydrogel (3D) to create a simplified tissue engineered stroma. The cells and tissues were exposed to hormone treatments mimicking early and late secretory phases, decidualization and steroid withdrawal conditions to recapitulate menstruation. Main Outcome Measure(s) Morphological and biochemical markers of decidualization and collagenase activity Result(s) The 3D tissue is capable of manifesting changes in morphology and biochemical markers of decidualization similar to 2D culture and characteristic of endometrial stroma in vivo. Unlike 2D culture, the 3D tissue responded to steroid withdrawal by increased collagenase activity and tissue breakdown. Conclusion(s) 3D tissue engineered endometrial stroma can mimic secretory and menstrual phases of the cycle and may be useful for studying uterine receptivity and menstruation in a physiological endocrine environment.

Tissue-engineered blood vessels may provide a solution to the lack of suitable blood vessels for coronary and peripheral vessel bypass grafting. Cyclic strain can be used to provide a more physiological environment that may result in tissue that more closely resembles native artery. In this study, cyclic strain is applied to a collagen-based, tissue-engineered vascular medium. An increased culture time was used to allow the tissue to adhere to the silastic sleeve and to eliminate longitudinal compaction. Cyclic strain improved tissue strength through increased collagen content as well as some radial tissue compaction. Mechanical stimulation promoted a more contractile phenotype and led to a greater contractile response to the vasoconstrictor endothelin-1.

Endometrial stromal and epithelial cell cross talk is known to influence many of the dynamic changes that occur during the menstrual cycle. We modified our previous model and embedded telomerase-immortalized human endometrial stromal cells and Ishikawa adenocarcinoma epithelial cells in a collagen-Matrigel hydrogel to create a tissue-engineered model of the endometrium. Comparisons of single and cocultured cells examined communication between endometrial stromal and epithelial cells, which were cultured with 0 or 10 nmol/L 17β estradiol; conditioned medium was used to look at the production of paracrine factors. Using this model, we were able to identify the changes in interleukin 6 (IL-6) and active matrix metalloproteinase 2, which appear to be due to paracrine signaling and differences in transforming growth factor β1 (TGF-β1) that do not appear to be due to paracrine signaling. Moreover, IL-6, TGF-β1, and DNA content were also affected by the presence of estradiol in many of the tissues. These results indicate that paracrine and endocrine signaling are involved in human endometrial responses and support the use of coculture models to further investigate cell-cell and cell-matrix interactions.

Over 6.5 million people in the United States suffer from traumatic, burn, acute, and chronic wounds yearly. When reconstruction is required, split and full-thickness autografts are a first line of treatment intervention. Negative pressure wound therapy (NPWT) is gaining traction as an adjunct modality to improve graft survival, yet the specifics on what settings to apply topically over the graft is unsubstantiated and associated with morbidities. This study was performed in an effort to understand initial changes in wound and graft healing with a long-term goal of surface pressure optimization. Excess skin from elective procedures from six human subjects was trimmed to 0.012 inch in order represent a split-thickness autografts. These grafts were treated continuously with either −75 mm Hg (n = 4), −125 mm Hg (n = 4), or no pressure (n = 4) for 3 hours. Six skin grafts were treated with no sponge or pressure control (n = 6). RNAseq was performed on all treatment groups and compared with no pressure control. Significant gene expression changes with a subset focusing on inflammatory, cellular/extracellular matrix proliferation and angiogenic mediators and having greater than 2-fold were confirmed with immunohistochemistry staining. There are 95 significant gene transcription differences among all treatment groups. NPWT leads to significantly increased gene expression of FGFR1, ET-1, and 22 Keratin proteins. Between −75 and −125 mm Hg groups, there are 19 significant gene changes. Proinflammatory genes S100A8 and Tenacin C (TNC) demonstrate an 8.8- and 9.1-fold change, respectively, and is upregulated in −125 mm Hg group and downregulated in −75 mm Hg group. Fibrinogen genes fibrinogen gamma chain and fibrinogen alpha chain had respective log2-fold changes of −7.9 and −7.4 change between treatment groups and were downregulated in −125 mm Hg group and upregulated in −75 mm Hg group. There are varying effects of surface pressures on human split-thickness autografts during the imbibition time period. NPWT may improve cellular migration, proliferation, and angiogenesis over controls. Human skin grafts respond differently to −125 and −75 mm Hg within 3 hours of NPWT treatment. The results suggest −75 mm Hg leads to less inflammation and increased fibrinogen production compared with the −125 mm Hg group, at least initially. Reducing “time to heal” with NPWT is critical to successful outcomes and quality of life within young patients who often experience pain/discomfort when treated at the current standard pump settings. The results from this study and continued investigation may quickly translate to the clinical setting by finding the ideal pressure setting utilized in an effort to reduce NPWT length of treatment, improve patient comfort, satisfaction, and psychosocial well-being.

Our data does not support a relationship between urinary neurotrophin levels and OAB in age-matched postmenopausal women. Further research is necessary to elucidate the role of urinary neurotrophins in the diagnosis and management of OAB. Neurourol. Urodynam. 36:740-744, 2017. © 2016 Wiley Periodicals, Inc.