The advent of the technology to isolate or generate human pluripotent stem cells provided the potential to develop a wide range of human models that could enhance understanding of mechanisms... Show moreThe advent of the technology to isolate or generate human pluripotent stem cells provided the potential to develop a wide range of human models that could enhance understanding of mechanisms underlying human development and disease. These systems are now beginning to mature and provide the basis for the development of in vitro assays suitable to understand the biological processes involved in the multi-organ systems of the human body, and will improve strategies for diagnosis, prevention, therapies and precision medicine. Induced pluripotent stem cell lines are prone to phenotypic and genotypic changes and donor/clone dependent vari-ability, which means that it is important to identify the most appropriate characterization markers and quality control measures when sourcing new cell lines and assessing differentiated cell and tissue culture preparations for experimental work. This paper considers those core quality control measures for human pluripotent stem cell lines and evaluates the state of play in the development of key functional markers for their differentiated cell derivatives to promote assurance of reproducibility of scientific data derived from pluripotent stem cell-based systems. Show less
Background: Robotic liver surgery represents the most recent evolution in the field of minimally-invasive liver surgery. For planning and guidance of liver resections, surgeons currently rely on... Show moreBackground: Robotic liver surgery represents the most recent evolution in the field of minimally-invasive liver surgery. For planning and guidance of liver resections, surgeons currently rely on preoperative 2-dimensional (2D) CT and/or MR imaging and intraoperative ultrasonography. Translating 2D images into digital 3-dimensional (3D) models may improve both preoperative planning and surgical guidance. The da Vinci (R) robotic surgical system is a platform suitable for the integration of multiple imaging modalities into one single view. In this study, we describe multimodal imaging options and introduce the Robotic Liver Surgery Cockpit; Methods: in-house developed software was used and validated for segmentation and registration to create a virtual reality 3D model of the liver based on preoperative imaging. The accuracy of the 3D models in the clinical setting was objectively assessed in 15 patients by measuring tumor diameters and subjectively with a postoperative conducted questionnaire; Results: Implementation and applicability of the 3D model in the surgical cockpit was feasible in all patients and the quality of the 3D reconstructions was high in 14 (93%) of cases. Tumor diameters measured on CT and/or MR imaging were comparable to automated measurements using the segmentation software and 3D models; Conclusions: the 3D model was successfully incorporated in the robotic surgery console as part of a multimodality imaging platform and aided the surgeon in planning and guidance of the resection. Future studies should focus on further automation of 3D rendering and progress into augmented reality. Show less
Polycystic kidney disease (PKD) is a prevalent genetic disorder, characterized by the formation of kidney cysts that progressively lead to kidney failure. The currently available drug tolvaptan is... Show morePolycystic kidney disease (PKD) is a prevalent genetic disorder, characterized by the formation of kidney cysts that progressively lead to kidney failure. The currently available drug tolvaptan is not well tolerated by all patients and there remains a strong need for alternative treatments. The signalling rewiring in PKD that drives cyst formation is highly complex and not fully understood. As a consequence, the effects of drugs are sometimes difficult to predict. We previously established a high-throughput microscopy phenotypic screening method for quantitative assessment of renal cyst growth. Here, we applied this 3D cyst growth phenotypic assay and screened 2320 small drug-like molecules, including approved drugs. We identified 81 active molecules that inhibit cyst growth. Multi-parametric phenotypic profiling of the effects on 3D cultured cysts discriminated molecules that showed preferred pharmacological effects above genuine toxicological properties. Celastrol, a triterpenoid from Tripterygium wilfordii, was identified as a potent inhibitor of cyst growth in vitro. In an in vivo iKspCre-Pkd1(lox,lox) mouse model for PKD, celastrol inhibited the growth of renal cysts and maintained kidney function. Show less
In recent years, there has been an increased interest in stem cells for the purpose of regenerative medicine to deliver a wide range of therapies to treat many diseases. However, two-dimensional... Show moreIn recent years, there has been an increased interest in stem cells for the purpose of regenerative medicine to deliver a wide range of therapies to treat many diseases. However, two-dimensional cultures of stem cells are of limited use when studying the mechanism of pathogenesis of diseases and the feasibility of a treatment. Therefore, research is focusing on the strengths of stem cells in the three-dimensional (3D) structures mimicking organs, that is, organoids, or organ-on-chip, for modeling human biology and disease. As 3D technology advances, it is necessary to know which signals stem cells need to multiply and differentiate into complex structures. This holds especially true for the complex 3D structure of the inner ear. Recent work suggests that although other factors play a role, the extracellular matrix (ECM), including its topography, is crucial to mimic a stem cell niche in vitro and to drive stem cells toward the formation of the tissue of interest. Technological developments have led to the investigation of biomaterials that closely resemble the native ECM. In the fast forward moving research of organoids and organs-on-chip, the inner ear has hardly received attention. This review aims to provide an overview, by describing the general context in which cells, matrix and morphogens cooperate in order to build a tissue, to facilitate research in 3D inner ear technology. Anat Rec, 303:408-426, 2020. (c) 2019 The Authors. The Anatomical Record published by Wiley Periodicals, Inc. on behalf of American Association of Anatomists. Show less
Polycystic kidney disease (PKD) is a prevalent genetic disorder, characterized by the formation of kidney cysts that progressively lead to kidney failure. The currently available drug tolvaptan is... Show morePolycystic kidney disease (PKD) is a prevalent genetic disorder, characterized by the formation of kidney cysts that progressively lead to kidney failure. The currently available drug tolvaptan is not well tolerated by all patients and there remains a strong need for alternative treatments. The signaling rewiring in PKD that drives cyst formation is highly complex and not fully understood. As a consequence, the effects of drugs are sometimes difficult to predict. We previously established a high throughput microscopy phenotypic screening method for quantitative assessment of renal cyst growth. Here, we applied this 3D cyst growth phenotypic assay and screened 2320 small drug-like molecules, including approved drugs. We identified 81 active molecules that inhibit cyst growth. Multi-parametric phenotypic profiling of the effects on 3D cultured cysts discriminated molecules that showed preferred pharmacological effects above genuine toxicological properties. Celastrol, a triterpenoid from Tripterygium Wilfordii, was identified as a potent inhibitor of cyst growth in vitro. In an in vivo iKspCre-Pkd1lox,lox mouse model for PKD, celastrol inhibited the growth of renal cysts and maintained kidney function. Show less
Gul, A.; Jong, M.A. de; Gijt, J.P. de; Wolvius, E.B.; Kayser, M.; Bohringer, S.; Koudstaal, M.J. 2019
Part I focuses on the potential role of 3-dimensional echocardiography. At first a clinical risk score model for prediction of outcome in patients undergoing TAVI is presented (Chapter 2). Second... Show morePart I focuses on the potential role of 3-dimensional echocardiography. At first a clinical risk score model for prediction of outcome in patients undergoing TAVI is presented (Chapter 2). Second the role of 3D-echocardiography is explored in depth in patients with mitral valve disease. Different non-invasive cardiac imaging modalities to evaluate mitral valve function and anatomy are described and the use of 3D-echocardiography is put into perspective (Chapter 3). We then evaluate the role of the latter to gain insights in patients with functional mitral regurgitation (Chapter 4), to select patients and guide procedures regarding percutaneous mitral valve repair using Mitra-Clip (Chapter 5) and to assess the effect of Mitra-Clip on the mitral valve (Chapter 6). In Part II we further elaborate the potential role of risk stratification by ECG and myocardial deformation imaging (strain), as surrogate markers of fibrosis. Surface ECG fragmentation in primary HCM is first evaluated (Chapter 7). The important future role of fibrosis imaging in valvular heart disease patients is then reviewed (Chapter 8). Finally the role of left atrial structure and function is evaluated in patients with mitral regurgitation (Chapter 9) and primary HCM (Chapter 10, 11). Show less
Eikendal, A.L.M.; Blomberg, B.A.; Haaring, C.; Saam, T.; Geest, R.J. van der; Visser, F.; ... ; Leiner, T. 2016
Bio-informatica kan omschreven worden als het toepassen van algoritmen om meerwaarde te verkrijgen uit data afkomstig van biomedisch en/of biologisch onderzoek. In bio-informatica wordt onderzoek... Show moreBio-informatica kan omschreven worden als het toepassen van algoritmen om meerwaarde te verkrijgen uit data afkomstig van biomedisch en/of biologisch onderzoek. In bio-informatica wordt onderzoek gedaan met grote gegevens verzamelingen die afkomstig zijn uit biomedisch en/of biologisch experimenten. Het doel van dit onderzoek is komen tot nieuwe inzichten vanuit de gegevens verzameling. Deze inzichten komen tot stand door de goede organisatie van de data, het linken naar en integreren met complementaire gegevens verzamelingen en ontwikkelen en toepassen van analytische methodieken. Als bio-informatica groep onderzoeken wij het inrichten en ontwikkelen van een 3D spatio-temporele data omgeving voor ontwikkelingsstudies van het zebravis model organisme. De expressie van genen in spatio-temporale patronen vormt de basis van het ontwikkelingsproces. Voor onderzoekers is een begrip van deze patronen in sam enhang met de anatomische ontwikkeling belangrijk; hoe vormen de patronen de basis voor vorm verandering en welke genen kunnen bij dergelijke veranderende patronen betrokken zijn. In deze context hebben wij een omgeving ontwikkeld voor spatio-temporele gegevens uit embryonische studies van het zebravis modelsysteem. Show less
