Human stem cells for cardiac disease modeling and preclinical and clinical applications—are we on the road to success?

Cardiovascular diseases (CVDs) are pointed out by the World Health Organization (WHO) as the leading cause of death, contributing to a significant and growing global health and economic burden. Despite advancements in clinical approaches, there is a critical need for innovative cardiovascular treatments to improve patient outcomes. Therapies based on adult stem cells (ASCs) and embryonic stem cells (ESCs) have emerged as promising strategies to regenerate damaged cardiac tissue and restore cardiac function. Moreover, the generation of human induced pluripotent stem cells (iPSCs) from somatic cells has opened new avenues for disease modeling, drug discovery, and regenerative medicine applications, with fewer ethical concerns than those associated with ESCs. Herein, we provide a state-of-the-art review on the application of human pluripotent stem cells in CVD research and clinics. We describe the types and sources of stem cells that have been tested in preclinical and clinical trials for the treatment of CVDs as well as the applications of pluripotent stem-cell-derived in vitro systems to mimic disease phenotypes. How human stem-cell-based in vitro systems can overcome the limitations of current toxicological studies is also discussed. Finally, the current state of clinical trials involving stem-cell-based approaches to treat CVDs are presented, and the strengths and weaknesses are critically discussed to assess whether researchers and clinicians are getting closer to success.B.M.S. was awarded with a Ph.D. fellowship (reference: 2022.13253.BDANA) by Fundação para a Ciência e Tecnologia (FCT). S.M.C is supported by a Stimulus of Scientific Employment, Individual Support (2020.01532.CEECIND) by FCT. J.B. is grateful to the FCT and the Comissão de Coordenação e Desenvolvimento Regional do Algarve (CCDR Algarve) for the project ALG-45-2020-41 and to Algarve Biomedical Center (ABC) for the award “Bolsa de Investigação Translacional—José Mariano Gago by ABC, 2022”. M.T.F. thanks the FCT for funding the project with the reference 2022.09209.PTDC.info:eu-repo/semantics/publishedVersio

Charting the path: navigating embryonic development to potentially safeguard against congenital heart defects

Congenital heart diseases (CHDs) are structural or functional defects present at birth due to improper heart development. Current therapeutic approaches to treating severe CHDs are primarily palliative surgical interventions during the peri- or prenatal stages, when the heart has fully developed from faulty embryogenesis. However, earlier interventions during embryonic development have the potential for better outcomes, as demonstrated by fetal cardiac interventions performed in utero, which have shown improved neonatal and prenatal survival rates, as well as reduced lifelong morbidity. Extensive research on heart development has identified key steps, cellular players, and the intricate network of signaling pathways and transcription factors governing cardiogenesis. Additionally, some reports have indicated that certain adverse genetic and environmental conditions leading to heart malformations and embryonic death may be amendable through the activation of alternative mechanisms. This review first highlights key molecular and cellular processes involved in heart development. Subsequently, it explores the potential for future therapeutic strategies, targeting early embryonic stages, to prevent CHDs, through the delivery of biomolecules or exosomes to compensate for faulty cardiogenic mechanisms. Implementing such non-surgical interventions during early gestation may offer a prophylactic approach toward reducing the occurrence and severity of CHDs.ALG-45-2020-41; 2022.13253.BDANAinfo:eu-repo/semantics/publishedVersio

A Multi-Scale Technique for . . .

We describe here an efficient algorithm for reassembling one or more unknown objects that have been broken or torn into a large number N of irregular fragments. The algorithm works by comparing the curvature-encoded fragment outlines, using a modified dynamic programming sequence-matching algorithm. By comparin

A Uniform Grid Structure To Speed Up Example-based Photometric Stereo.

In this paper, we describe a data structure and an algorithm to accelerate the table lookup step in example-based multiimage photometric stereo. In that step, one must find a pixel of a reference object, of known shape and color, whose appearance under m different illumination fields is similar to that of a given scene pixel. This search reduces to finding the closest match to a given m-vector in a table with a thousand or more m-vectors. Our method is faster than previously known solutions for this problem but, unlike some of them, is exact, i.e., always yields the best matching entry in the table, and does not assume point-like sources. Our solution exploits the fact that the table is in fact a fairly flat 2-D manifold in m-dimensional space so that the search can be efficiently solved with a uniform 2-D grid structure.203495-50

Necro-inflammatory activity grading in chronic viral hepatitis with three-dimensional multifrequency MR elastography

International audienceAbstract The purpose of this study was to assess the diagnostic value of multifrequency MR elastography for grading necro-inflammation in the liver. Fifty participants with chronic hepatitis B or C were recruited for this institutional review board-approved study. Their liver was examined with multifrequency MR elastography. The storage, shear and loss moduli, and the damping ratio were measured at 56 Hz. The multifrequency wave dispersion coefficient of the shear modulus was calculated. The measurements were compared to reference markers of necro-inflammation and fibrosis with Spearman correlations and multiple regression analysis. Diagnostic accuracy was assessed. At multiple regression analysis, necro-inflammation was the only determinant of the multifrequency dispersion coefficient, whereas fibrosis was the only determinant of the storage, loss and shear moduli. The multifrequency dispersion coefficient had the largest AUC for necro-inflammatory activity A ≥ 2 [0.84 (0.71–0.93) vs. storage modulus AUC: 0.65 (0.50–0.79), p = 0.03], whereas the storage modulus had the largest AUC for fibrosis F ≥ 2 [AUC (95% confidence intervals) 0.91 (0.79–0.98)] and cirrhosis F4 [0.97 (0.88–1.00)]. The measurement of the multifrequency dispersion coefficient at three-dimensional MR elastography has the potential to grade liver necro-inflammation in patients with chronic vial hepatitis

Wettability-Assisted Process to Shape Organic Crystalline Printed Films

The controlled growth of organic crystalline materials in predefined locations still poses a challenge for functional device application such as phototransistors, photoconductors, or photovoltaic solar cells. This work evidences the use of optical lithography and a fluoroalkylsilane to selectively modify the surface energy and how to create a wettability micro-patterned structure. These are then combined with non-contact printing of the organic solution providing custom-shaped films. To deliver printed films with improved morphological quality, key process parameters for high-performance organic materials are optimized. Particular attention is given to the adjustment of the concentration and solvent mixture to tune the jetting properties, and consequently, slow down the evaporation rate. Continuous films are obtained for an optimized number of droplets and spacing between them. Micro-Raman spectroscopy imaging confirms the crystalline nature of the printed films and the lack of impurities. To validate the method, rubrene and triisopropylsilylethynyl (TIPS)-pentacene are tested using two-terminal optoelectronic devices. TIPS-pentacene rectangular printed micrometric photosensor presents linear behavior and no hysteresis, reaching 0.33 nA under 18.1 mW cm−2. The structural and optoelectronic characterization is in line with other micro-patterned examples, opening doors for new industrial applications

MR elastography of liver tumours:value of viscoelastic properties for tumour characterisation

International audienceOBJECTIVES: To assess the value of the viscoelastic parameters in the characterisation of liver tumours at MR elastography. PATIENTS AND METHODS: Ninety-four patients with liver tumours >1 cm prospectively underwent MR elastography using 50-Hz mechanical waves and a full three-directional motion-sensitive sequence. The model-free viscoelastic parameters (the complex shear modulus and its real and imaginary parts, i.e. the storage and loss moduli) were calculated in 72 lesions after exclusion of cystic, treated or histopathologically undetermined tumours. RESULTS: We observed higher absolute shear modulus and loss modulus in malignant versus benign tumours (3.38 ± 0.26 versus 2.41 ± 0.15 kPa, P < 0.01 and 2.25 ± 0.26 versus 1.05 ± 0.13 kPa, P < 0.001, respectively). Moreover, the loss modulus of hepatocellular carcinomas was significantly higher than in benign hepatocellular tumours. The storage modulus did not differ significantly between malignant and benign tumours. The area under the receiver-operating characteristic curve of loss modulus was significantly larger than that of the absolute shear modulus and storage modulus when comparing malignant and benign lesions. CONCLUSIONS: The increased loss modulus is a better discriminator between benign and malignant tumours than the increased storage modulus or absolute value of the shear modulus. KEY POINTS : * Magnetic Resonance elastography is a new method of assessing the liver. * Increased loss modulus is an indicator of malignancy in hepatic tumours. * Loss modulus is a better discriminator than absolute shear modulus values. * The viscoelastic properties of lesions offer promise for characterising liver tumours