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Angiogenesis Nov 2023Following the process of vasculogenesis during development, angiogenesis generates new vascular structures through a variety of different mechanisms or modes. These...
Following the process of vasculogenesis during development, angiogenesis generates new vascular structures through a variety of different mechanisms or modes. These different modes of angiogenesis involve, for example, increasing microvasculature density by sprouting of endothelial cells, splitting of vessels to increase vascular surface area by intussusceptive angiogenesis, fusion of capillaries to increase blood flow by coalescent angiogenesis, and the recruitment of non-endothelial cells by vasculogenic mimicry. The recent reporting on coalescent angiogenesis as a new mode of vessel formation warrants a brief overview of angiogenesis mechanisms to provide a more complete picture. The journal Angiogenesis is devoted to the delineation of the different modes and mechanisms that collectively dictate blood vessel formation, inhibition, and function in health and disease.
Topics: Neovascularization, Physiologic; Endothelial Cells; Capillaries; Morphogenesis
PubMed: 37640982
DOI: 10.1007/s10456-023-09895-4 -
BioRxiv : the Preprint Server For... Oct 2023Engineering functional tissues and organs remains a fundamental pursuit in biofabrication. However, the accurate constitution of complex shapes and internal anatomical...
Engineering functional tissues and organs remains a fundamental pursuit in biofabrication. However, the accurate constitution of complex shapes and internal anatomical features of specific organs, including their intricate blood vessels and nerves, remains a significant challenge. Inspired by the Matryoshka doll, we here introduce a new method called 'Intra-Embedded Bioprinting (IEB),' building upon existing embedded bioprinting methods. We used a xanthan gum-based material, which served a dual role as both a bioprintable ink and a support bath, due to its unique shear-thinning and self-healing properties. We demonstrated IEB's capabilities in organ modelling, creating a miniaturized replica of a pancreas using a photocrosslinkable silicone composite. Further, a head phantom and a Matryoshka doll were 3D printed, exemplifying IEB's capability to manufacture intricate, nested structures. Towards the use case of IEB and employing innovative coupling strategy between extrusion-based and aspiration-assisted bioprinting, we developed a breast tumor model that included a central channel mimicking a blood vessel, with tumor spheroids bioprinted in proximity. Validation using a clinically-available chemotherapeutic drug illustrated its efficacy in reducing the tumor volume via perfusion over time. This method opens a new way of bioprinting enabling the creation of complex-shaped organs with internal anatomical features.
PubMed: 37808743
DOI: 10.1101/2023.09.28.560028 -
Stem Cell Research & Therapy Oct 2023Understanding mechanisms and manifestations of cardiovascular risk factors, including diabetes, on vascular cells such as endothelial cells, pericytes, and vascular... (Review)
Review
Understanding mechanisms and manifestations of cardiovascular risk factors, including diabetes, on vascular cells such as endothelial cells, pericytes, and vascular smooth muscle cells, remains elusive partly due to the lack of appropriate disease models. Therefore, here we explore different aspects for the development of advanced 3D in vitro disease models that recapitulate human blood vessel complications using patient-derived induced pluripotent stem cells, which retain the epigenetic, transcriptomic, and metabolic memory of their patient-of-origin. In this review, we highlight the superiority of 3D blood vessel organoids over conventional 2D cell culture systems for vascular research. We outline the key benefits of vascular organoids in both health and disease contexts and discuss the current challenges associated with organoid technology, providing potential solutions. Furthermore, we discuss the diverse applications of vascular organoids and emphasize the importance of incorporating all relevant cellular components in a 3D model to accurately recapitulate vascular pathophysiology. As a specific example, we present a comprehensive overview of diabetic vasculopathy, demonstrating how the interplay of different vascular cell types is critical for the successful modelling of complex disease processes in vitro. Finally, we propose a strategy for creating an organ-specific diabetic vasculopathy model, serving as a valuable template for modelling other types of vascular complications in cardiovascular diseases by incorporating disease-specific stressors and organotypic modifications.
Topics: Humans; Endothelial Cells; Organoids; Induced Pluripotent Stem Cells; Pericytes; Diabetes Mellitus
PubMed: 37817281
DOI: 10.1186/s13287-023-03521-2 -
Bioengineering (Basel, Switzerland) Jun 2023The precise display of blood vessel information for doctors is crucial. This is not only true for facilitating intravenous injections, but also for the diagnosis and...
The precise display of blood vessel information for doctors is crucial. This is not only true for facilitating intravenous injections, but also for the diagnosis and analysis of diseases. Currently, infrared cameras can be used to capture images of superficial blood vessels. However, their imaging quality always has the problems of noises, breaks, and uneven vascular information. In order to overcome these problems, this paper proposes an image segmentation algorithm based on the background subtraction and improved mathematical morphology. The algorithm regards the image as a superposition of blood vessels into the background, removes the noise by calculating the size of connected domains, achieves uniform blood vessel width, and smooths edges that reflect the actual blood vessel state. The algorithm is evaluated subjectively and objectively in this paper to provide a basis for vascular image quality assessment. Extensive experimental results demonstrate that the proposed method can effectively extract accurate and clear vascular information.
PubMed: 37370657
DOI: 10.3390/bioengineering10060726 -
Sensors (Basel, Switzerland) Dec 2023This review outlines the latest methods and innovations for assessing arterial stiffness, along with their respective advantages and disadvantages. Furthermore, we... (Review)
Review
This review outlines the latest methods and innovations for assessing arterial stiffness, along with their respective advantages and disadvantages. Furthermore, we present compelling evidence indicating a recent growth in research focused on assessing arterial stiffness using photoplethysmography (PPG) and propose PPG as a potential tool for assessing vascular ageing in the future. Blood vessels deteriorate with age, losing elasticity and forming deposits. This raises the likelihood of developing cardiovascular disease (CVD), widely reported as the global leading cause of death. The ageing process induces structural modifications in the vascular system, such as increased arterial stiffness, which can cause various volumetric, mechanical, and haemodynamic alterations. Numerous techniques have been investigated to assess arterial stiffness, some of which are currently used in commercial medical devices and some, such as PPG, of which still remain in the research space.
Topics: Humans; Photoplethysmography; Vascular Stiffness; Cardiovascular Diseases; Aging; Arteries
PubMed: 38139728
DOI: 10.3390/s23249882 -
Cyborg and Bionic Systems (Washington,... 2023Dysfunctional blood vessels are implicated in various diseases, including cardiovascular diseases, neurodegenerative diseases, and cancer. Several studies have attempted... (Review)
Review
Dysfunctional blood vessels are implicated in various diseases, including cardiovascular diseases, neurodegenerative diseases, and cancer. Several studies have attempted to prevent and treat vascular diseases and understand interactions between these diseases and blood vessels across different organs and tissues. Initial studies were conducted using 2-dimensional (2D) in vitro and animal models. However, these models have difficulties in mimicking the 3D microenvironment in human, simulating kinetics related to cell activities, and replicating human pathophysiology; in addition, 3D models involve remarkably high costs. Thus, in vitro bioengineered models (BMs) have recently gained attention. BMs created through biofabrication based on tissue engineering and regenerative medicine are breakthrough models that can overcome limitations of 2D and animal models. They can also simulate the natural microenvironment in a patient- and target-specific manner. In this review, we will introduce 3D bioprinting methods for fabricating bioengineered blood vessel models, which can serve as the basis for treating and preventing various vascular diseases. Additionally, we will describe possible advancements from tubular to vascular models. Last, we will discuss specific applications, limitations, and future perspectives of fabricated BMs.
PubMed: 37533545
DOI: 10.34133/cbsystems.0043 -
Scientific Reports Sep 2023Vessel segmentation in fundus images permits understanding retinal diseases and computing image-based biomarkers. However, manual vessel segmentation is a time-consuming...
Vessel segmentation in fundus images permits understanding retinal diseases and computing image-based biomarkers. However, manual vessel segmentation is a time-consuming process. Optical coherence tomography angiography (OCT-A) allows direct, non-invasive estimation of retinal vessels. Unfortunately, compared to fundus images, OCT-A cameras are more expensive, less portable, and have a reduced field of view. We present an automated strategy relying on generative adversarial networks to create vascular maps from fundus images without training using manual vessel segmentation maps. Further post-processing used for standard en face OCT-A allows obtaining a vessel segmentation map. We compare our approach to state-of-the-art vessel segmentation algorithms trained on manual vessel segmentation maps and vessel segmentations derived from OCT-A. We evaluate them from an automatic vascular segmentation perspective and as vessel density estimators, i.e., the most common imaging biomarker for OCT-A used in studies. Using OCT-A as a training target over manual vessel delineations yields improved vascular maps for the optic disc area and compares to the best-performing vessel segmentation algorithm in the macular region. This technique could reduce the cost and effort incurred when training vessel segmentation algorithms. To incentivize research in this field, we will make the dataset publicly available to the scientific community.
Topics: Tomography, Optical Coherence; Angiography; Fundus Oculi; Retinal Vessels; Optic Disk
PubMed: 37714881
DOI: 10.1038/s41598-023-42062-9 -
Biomedicine & Pharmacotherapy =... Aug 2023Cancer remains a formidable global health challenge, and as such, investigators are constantly exploring underlying mechanisms that drive its progression. One area of... (Review)
Review
Cancer remains a formidable global health challenge, and as such, investigators are constantly exploring underlying mechanisms that drive its progression. One area of interest is the role of lysosomal enzymes, such as cathepsins, in regulating cancer growth and development in the tumour microenvironment (TME). Pericytes, a key component of vasculature, play a key role in regulating blood vessel formation in the TME, have been shown to be influenced by cathepsins and their activity. Although cathepsins such as cathepsins D and L have been shown to induce angiogenesis, currently no direct link is known between pericytes and cathepsins interaction. This review aims to shed light on the potential interplay between pericytes and cathepsins in the TME, highlighting the possible implications for cancer therapy and future research directions.
Topics: Humans; Pericytes; Cathepsins; Tumor Microenvironment; Neoplasms
PubMed: 37236029
DOI: 10.1016/j.biopha.2023.114932 -
Scientific Reports Aug 2023Endothelial cells cover the lining of different blood vessels and lymph nodes, and have major functions including the transport of blood, vessel homeostasis,...
Endothelial cells cover the lining of different blood vessels and lymph nodes, and have major functions including the transport of blood, vessel homeostasis, inflammatory responses, control of transendothelial migration of circulating cells into the tissues, and formation of new blood vessels. Therefore, understanding these cells is of major interest. The morphological features, phenotype and function of endothelial cells varies according to the vascular bed examined. The sialomucin, CD34, is widely used as an endothelial marker. However, CD34 is differentially expressed on endothelial cells in different organs and in pathological conditions. Little is known about regulation of endothelial CD34 expression or function. Expression of CD34 is also strongly regulated in-vitro in endothelial cell models, including human umbilical vein endothelial cells (HUVEC) and endothelial colony forming cells (ECFC). We have therefore analysed the expression and function of CD34 by comparing CD34 and CD34 endothelial cell subpopulations. Transcriptomic analysis showed that CD34 gene and protein expressions are highly correlated, that CD34 cells proliferate less but express higher levels of IL-33 and Angiopoietin 2, compared with CD34 cells. Higher secretion levels of IL-33 and Angiopoietin 2 by CD34 HUVECs was confirmed by ELISA. Finally, when endothelial cells were allowed to interact with peripheral blood mononuclear cells, CD34 endothelial cells activated stronger proliferation of regulatory T lymphocytes (Tregs) compared to CD34 cells whereas expansion of other CD4-T cell subsets was equivalent. These results suggest that CD34 expression by endothelial cells in-vitro associates with their ability to proliferate and with an immunogenic ability that favours the tolerogenic response.
Topics: Humans; Angiopoietin-2; Interleukin-33; Leukocytes, Mononuclear; Antigens, CD34; Cell Adhesion Molecules; Human Umbilical Vein Endothelial Cells
PubMed: 37598252
DOI: 10.1038/s41598-023-40622-7 -
Eye (London, England) Aug 2023Cerebral malaria (CM) remains a common cause of death of children in Africa with annual mortality of 400 000. Malarial retinopathy is a unique set of fundus signs which... (Review)
Review
Cerebral malaria (CM) remains a common cause of death of children in Africa with annual mortality of 400 000. Malarial retinopathy is a unique set of fundus signs which has diagnostic and prognostic value in CM. Assessment of malarial retinopathy is now widely utilised in clinical care, and routinely incorporated into clinical studies to refine entry criteria. As a visible part of the central nervous system, the retina provides insights into the pathophysiology of this infectious small-vessel vasculitis with adherent parasitised red blood cells. Fluorescein angiography and optical coherence tomography (OCT) have shown that patchy capillary non-perfusion is common and causes ischaemic changes in the retina in CM. It is likely this is mirrored in the brain and may cause global neurological impairments evident on developmental follow up. Three types of blood-retina barrier breakdown are evident: large focal, punctate, and vessel leak. Punctate and large focal leak (haemorrhage in formation) are associated with severe brain swelling and fatal outcome. Vessel leak and capillary non-perfusion are associated with moderate brain swelling and neurological sequelae. These findings imply that death and neurological sequelae have separate mechanisms and are not a continuum of severity. Each haemorrhage causes a temporary uncontrolled outflow of fluid into the tissue. The rapid accumulation of haemorrhages, as evidenced by multiple focal leaks, is a proposed mechanism of severe brain swelling, and death. Current studies aim to use optic nerve head OCT to identify patients with severe brain swelling, and macula OCT to identify those at risk of neurological sequelae.
Topics: Child; Humans; Malaria, Cerebral; Brain Edema; Retina; Retinal Diseases; Brain; Fluorescein Angiography; Tomography, Optical Coherence; Retinal Vessels
PubMed: 36788363
DOI: 10.1038/s41433-023-02432-z