Luminal Chemosensory Cells in the Small Intestine

In addition to the small intestine’s well-known function of nutrient absorption, the small intestine also plays a major role in nutrient sensing. Similar to taste sensors seen on the tongue, GPCR-coupled nutrient sensors are expressed throughout the intestinal epithelium and respond to nutrients found in the lumen. These taste receptors respond to specific ligands, such as digested carbohydrates, fats, and proteins. The activation of nutrient sensors in the intestine allows for the induction of signaling pathways needed for the digestive system to process an influx of nutrients. Such processes include those related to glucose homeostasis and satiety. Defects in intestinal nutrient sensing have been linked to a variety of metabolic disorders, such as type 2 diabetes and obesity. Here, we review recent updates in the mechanisms related to intestinal nutrient sensors, particularly in enteroendocrine cells, and their pathological roles in disease. Additionally, we highlight the emerging nutrient sensing role of tuft cells and recent work using enteroids as a sensory organ model.

A Method for the Evaluation of Early Osseointegration of Implant Materials Ex Vivo: Human Bone Organ Model

In the present work, an ex vivo organ model using human bone (explant) was developed for the evaluation of the initial osseointegration behavior of implant materials. The model was tested with additive manufactured Ti6Al4V test substrates with different 3D geometries. Explants were obtained from patients who underwent total knee replacement surgery. The tibial plateaus were used within 24 h after surgery to harvest bone cylinders (BC) from the anterior side using hollow burrs. The BCs were brought into contact with the test substrate and inserted into an agarose mold, then covered with cell culture media and subjected to the external load of 500 g. Incubation was performed for 28 days. After 28d the test substrate was removed for further analysis. Cells grown out BC onto substrate were immunostained with DAPI and with an antibody against Collagen-I and alkaline phosphatase (ALP) for visualization and cell counting. We show that cells stayed alive for up to 28d in our organ model. The geometry of test substrates influences the number of cells grown onto substrate from BCs. The model presented here can be used for testing implant materials as an alternative for in vitro tests and animal models.

Development of a constant pressure perfused ex vivo model of the equine larynx

Distal axonopathy is seen in a broad range of species including equine patients. In horses, this degenerative disorder of the recurrent laryngeal nerve is described as recurrent laryngeal neuropathy (RLN). The dysfunctional innervation of the cricoarytenoideus dorsalis muscle (CAD) leads to a loss of performance in affected horses. In general, ex vivo models of the larynx are rare and for equine patients, just one short report is available. To allow for testing new therapy approaches in an isolated organ model, we examined equine larynges in a constant pressure perfused setup. In order to check the vitality and functionality of the isolated larynx, the vessels´ reaction to norepinephrine (NE) and sodium nitroprusside (NP) as vasoactive agents was tested. Additionally, the contractility of the CAD was checked via electrical stimulation. To determine the extent of hypoxic alterations, lactate dehydrogenase (LDH) and lactate were measured and an immunofluorescent analysis of hypoxia-inducible factor (HIF-1α), a key transcription factor in hypoxia, was performed. For this, a hypoxia-induced cell culture for HIF-1α was developed. The application of NE led to an expected vasoconstriction while NP caused the expected vasodilation. During a perfusion period of 352 ±20.78 min, LDH values were in the reference range and lactate values slightly exceeded the reference range at the end of the perfusion. HIF-1α nuclear translocation could reliably be detected in the hypoxia-induced cell cultures, but not in sections of the perfused CAD. With the approach presented here, a solid basis for perfusing equine larynges was established and may serve as a tool for further investigations of equine larynx disorders as well as a transferrable model for other species.

Hormone autocrination by vascularized hydrogel delivery of ovary spheroids to rescue ovarian dysfunctions

The regeneration potential of implantable organ model hydrogels is applied to treat a loss of ovarian endocrine function in women experiencing menopause and/or cancer therapy. A rat ovariectomy model is used to harvest autologous ovary cells while subsequently producing a layer-by-layer form of follicle spheroids. Implantation of a microchannel network hydrogel with cell spheroids [vascularized hydrogel with ovarian spheroids (VHOS)] into an ischemic hindlimb of ovariectomized rats significantly aids the recovery of endocrine function with hormone release, leading to full endometrium regeneration. The VHOS implantation effectively suppresses the side effects observed with synthetic hormone treatment (i.e., tissue overgrowth, hyperplasia, cancer progression, deep vein thrombosis) to the normal levels, while effectively preventing the representative aftereffects of menopause (i.e., gaining fatty weight, inducing osteoporosis). These results highlight the unprecedented therapeutic potential of an implantable VHOS against menopause and suggest that it may be used as an alternative approach to standard hormone therapy.

3D Shared Matting Method for Directly Extracting Standard Organ Models from Human Body Color Volume Image

Background: In some medical applications (e.g., virtual surgery), standard human organ models are very important and useful. Now that real human body slice image sets have been collected by several countries, it is possible to obtain real standard organ models. Introduction: Understanding how to abandon the traditional model construction method of Photoshop sketching slice by slice and directly extracting 3D models from volume images has been an interesting and challenging issue. In this paper, a 3D color volume image matting method has been proposed to segment human body organ models. Methods: First, the scope of the known area will be expanded by means of propagation. Next, neighborhood sampling to find the best sampling for voxels in an unknown region will be performed and then the preliminary opacity using the sampling results will be calculated. Results: The final result will be obtained by applying local smoothing to the image. Conclusion: From the experimental results, it has been observed that our method is effective for real standard organ model extraction.

A mathematical multi-organ model for bidirectional epithelial–mesenchymal transitions in the metastatic spread of cancer

Cancer invasion and metastatic spread to secondary sites in the body are facilitated by a complex interplay between cancer cells of different phenotypes and their microenvironment. A trade-off between the cancer cells’ ability to invade the tissue and to metastasize, and their ability to proliferate has been observed. This gives rise to the classification of cancer cells into those of mesenchymal and epithelial phenotype, respectively. Additionally, mixed phenotypic states between these two extremes exist. Cancer cells can transit between these states via epithelial–mesenchymal transition (EMT) and the reverse process, mesenchymal–epithelial transition (MET). These processes are crucial for both the local tissue invasion and the metastatic spread of cancer cells. To shed light on the role of these phenotypic states and the transitions between them in the invasive and metastatic process, we extend our recently published multi-grid, hybrid, individual-based mathematical metastasis framework (Franssen et al. 2019, A mathematical framework for modelling the metastatic spread of cancer. Bull. Math. Biol., 81, 1965). In addition to cancer cells of epithelial and of mesenchymal phenotype, we now also include those of an intermediate partial-EMT phenotype. Furthermore, we allow for the switching between these phenotypic states via EMT and MET at the biologically appropriate steps of the invasion-metastasis cascade. We also account for the likelihood of spread of cancer cells to the various secondary sites and differentiate between the tissues of the organs involved in our simulations. Finally, we consider the maladaptation of metastasized cancer cells to the new tumour microenvironment at secondary sites as well as the immune response at these sites by accounting for cancer cell dormancy and death. This way, we create a first mathematical multi-organ model that explicitly accounts for EMT-processes occurring at the level of individual cancer cells in the context of the invasion-metastasis cascade.

The establishment of the first ex vivo whole organ model for human liver neoplasms

Background: The incidence of liver neoplasms is on the leading rise worldwide due to lacking exact research model. Accordingly, the resected diseased liver within cancer during liver transplantation was the appropriated model, therefore the aim of this study was to establish the first ex vivo whole organ model for liver neoplasms by using normothermic perfusion system named Life-X system. Materials and Methods: Four diseased livers within cancer resected during liver transplantation were collected for research. The common hepatic artery and portal vein of the ex vivo liver were connected to the Life-X perfusion device that circulated Life-X perfusate providing continuous oxygen and nutrient supply. The flow and pressure of the perfusate was recorded and blood gas analysis was examined to analyze the function of the diseased liver. Liver tissues after perfusion were collected for histological analysis. Results: Experiments showed that the artery and portal vein flow were stable 1h after perfusion and were kept within the physiological range. The results of blood gas analysis demonstrated restoration and maintenance of metabolism. Moreover, the bile production of diseased Case 4 liver represented its vivid functionality during the entire 47h of perfusion. Histology analysis shows little liver injury after the perfusion. Conclusions: Therefore, we have established a powerful tool to research liver neoplasms in vitro through Life-X perfusion system.