Three-dimensional microengineered vascularised endometrium-on-a-chip.

STUDY QUESTION: Can we reconstitute physiologically relevant 3-dimensional (3D) microengineered endometrium in-vitro model? SUMMARY ANSWER: Our representative microengineered vascularised endometrium on-a-chip closely recapitulates the endometrial microenvironment that consists of three distinct layers including epithelial cells, stromal fibroblasts and endothelial cells in a 3D extracellular matrix in a spatiotemporal manner. WHAT IS KNOWN ALREADY: Organ-on-a-chip, a multi-channel 3D microfluidic cell culture system, is widely used to investigate physiologically relevant responses of organ systems. STUDY DESIGN, SIZE, DURATION: The device consists of five microchannels that are arrayed in parallel and partitioned by array of micropost. Two central channels are for 3D culture and morphogenesis of stromal fibroblast and endothelial cells. In addition, the outermost channel is for the culture of additional endometrial stromal fibroblasts that secrete biochemical cues to induce directional pro-angiogenic responses of endothelial cells. To seed endometrial epithelial cells, on Day 8, Ishikawa cells were introduced to one of the two medium channels to adhere on the gel surface. After that, the microengineered endometrium was cultured for an additional 5-6 days (total ∼ 14 days) for the purpose of each experiment. PARTICIPANTS/MATERIALS, SETTING, METHODS: Microfluidic 3D cultures were maintained in endothelial growth Medium 2 with or without oestradiol and progesterone. Some cultures additionally received exogenous pro-angiogenic factors. For the three distinct layers of microengineered endometrium-on-a-chip, the epithelium, stroma and blood vessel characteristics and drug response of each distinct layer in the microfluidic model were assessed morphologically and biochemically. The quantitative measurement of endometrial drug delivery was evaluated by the permeability coefficients. MAIN RESULTS AND THE ROLE OF CHANCE: We established microengineered vascularised endometrium-on-chip, which consists of three distinct layers: epithelium, stroma and blood vessels. Our endometrium model faithfully recapitulates in-vivo endometrial vasculo-angiogenesis and hormonal responses displaying key features of the proliferative and secretory phases of the menstrual cycle. Furthermore, the effect of the emergency contraception drug levonorgestrel was evaluated in our model demonstrating increased endometrial permeability and blood vessel regression in a dose-dependent manner. We finally provided a proof of concept of the multi-layered endometrium model for embryo implantation, which aids a better understanding of the molecular and cellular mechanisms underlying this process. LARGE SCALE DATA: N/A. LIMITATIONS, REASONS FOR CAUTION: This report is largely an in-vitro study and it would be beneficial to validate our findings using human primary endometrial cells. WIDER IMPLICATIONS OF THE FINDINGS: Our 3D microengineered vascularised endometrium-on-a-chip provides a new in-vitro approach to drug screening and drug discovery by mimicking the complicated behaviours of human endometrium. Thus, we suggest our model as a tool for addressing critical challenges and unsolved problems in female diseases, such as endometriosis, uterine cancer and female infertility, in a personalised manner. STUDY FUNDING/COMPETING INTEREST(S): This work is supported by funding from the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT) to Y.J.K. (No. 2018R1C1B6003), to J.A. (No. 2020R1I1A1A01074136) and to H.S.K. (No. 2020R1C1C100787212). The authors report no conflicts of interest.

Study on the structural and photocatalytic properties for pore size tailored SnO2-pillared layered titanate nanohybrids.

A new mesoporous SnO2-pillared layered titanate is prepared by hybridizing the exfoliated titanate nanosheets with SnO2 nanosol particles. The pore size tailored porous nanohybrids (SBET = 74 approximately 280 m2/g and d = 18 approximately 96 angstroms) are obtained after calcining an as-prepared sample. The mesoporous nanohybrids exhibited different photocatalytic behaviors for salicylic acid and methylene blue depending upon their crystallinity and porous structure.

CXCL12 enhances pregnancy outcome via improvement of endometrial receptivity in mice.

Successful pregnancy inevitably depends on the implantation of a competent embryo into a receptive endometrium. Although many substances have been suggested to improve the rate of embryo implantation targeting enhancement of endometrial receptivity, currently there rarely are effective evidence-based treatments to prevent or cure this condition. Here we strongly suggest minimally-invasive intra-uterine administration of embryo-secreted chemokine CXCL12 as an effective therapeutic intervention. Chemokine CXCL12 derived from pre- and peri-implanting embryos significantly enhances the rates of embryo attachment and promoted endothelial vessel formation and sprouting in vitro. Consistently, intra-uterine CXCL12 administration in C57BL/6 mice improved endometrial receptivity showing increased integrin ß3 and its ligand osteopontin, and induced endometrial angiogenesis displaying increased numbers of vessel formation near the lining of endometrial epithelial layer with higher CD31 and CD34 expression. Furthermore, intra-uterine CXCL12 application dramatically promoted the rates of embryo implantation with no morphologically retarded embryos. Thus, our present study provides a novel evidence that improved uterine endometrial receptivity and enhanced angiogenesis induced by embryo-derived chemokine CXCL12 may aid to develop a minimally-invasive therapeutic strategy for clinical treatment or supplement for the patients with repeated implantation failure with less risk.

Pathological Evaluation of Radiation-Induced Vascular Lesions of the Brain: Distinct from De Novo Cavernous Hemangioma.

PURPOSE: We aimed to evaluate the histologic and radiologic findings of vascular lesions after stereotactic radiosurgery (SRS) categorized as radiation-induced cavernous hemangioma (RICH). MATERIALS AND METHODS: Among 89 patients who underwent neurosurgery for cavernous hemangioma, eight RICHs from 7 patients and 10 de novo CHs from 10 patients were selected for histopathological and radiological comparison. RESULTS: Histologically, RICHs showed hematoma-like gross appearance. Microscopically, RICH exhibited a hematoma-like area accompanied by proliferation of thin-walled vasculature with fibrin deposits and infiltrating foamy macrophages. In contrast, CHs demonstrated localized malformed vasculature containing fresh and old clotted blood on gross examination. Typically, CHs consisted of thick, ectatic hyalinized vessels lined by endothelium under a light microscope. Magnetic resonance imaging of RICHs revealed some overlapping but distinct features with CHs, including enhancing cystic and solid components with absence or incomplete popcorn-like appearance and partial hemosiderin rims. CONCLUSION: Together with histologic and radiologic findings, RICH may result from blood-filled space after tissue destruction by SRS, accompanied with radiation-induced reactive changes rather than vascular malformation. Thus, the term "RICH" would be inappropriate, because it is more likely to be an inactive organizing hematoma rather than proliferation of malformed vasculature.

Analysis of cyclic pyrolysis products formed from amino acid monomer.

Amino acid was mixed with silica and tetramethylammonium hydroxide (TMAH) to favor pyrolysis of amino acid monomer. The pyrolysis products formed from amino acid monomer were using GC/MS and GC. 20 amino acids of alanine, arginine, asparagine, aspartic acid, cysteine, glutamic acid, glutamine, glycine, histidine, isoleucine, leucine, lysine, methionine, phenylalanine, proline, serine, threonine, tryptophan, tyrosine, and valine were analyzed. The pyrolysis products were divided into cyclic and non-cyclic products. Among the 20 amino acids, arginine, asparagine, glutamic acid, glutamine, histidine, lysine, and phenylalanine generated cyclic pyrolysis products of the monomer. New cyclic pyrolysis products were formed by isolation of amino acid monomers. They commonly had polar side functional groups to 5-, 6-, or 7-membered ring structure. Arginine, asparagine, glutamic acid, glutamine, histidine, and phenylalanine generated only 5- or 6-membered ring products. However, lysine generated both 6- and 7-membered ring compounds. Variations of the relative intensities of the cyclic pyrolysis products with the pyrolysis temperature and amino acid concentration were also investigated.