scholarly journals Imaging the Renal Microcirculation in Cell Therapy

Cells ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 1087
Author(s):  
Katerina Apelt ◽  
Roel Bijkerk ◽  
Franck Lebrin ◽  
Ton J. Rabelink
Keyword(s):  
Kidney Disease ◽  
Renal Disease ◽  
Current Knowledge ◽  
Imaging Techniques ◽  
Renal Microcirculation ◽  
Microvascular Changes ◽  
Cell Based Therapy ◽  
The Moment ◽  
And Behavior

Renal microvascular rarefaction plays a pivotal role in progressive kidney disease. Therefore, modalities to visualize the microcirculation of the kidney will increase our understanding of disease mechanisms and consequently may provide new approaches for evaluating cell-based therapy. At the moment, however, clinical practice is lacking non-invasive, safe, and efficient imaging modalities to monitor renal microvascular changes over time in patients suffering from renal disease. To emphasize the importance, we summarize current knowledge of the renal microcirculation and discussed the involvement in progressive kidney disease. Moreover, an overview of available imaging techniques to uncover renal microvascular morphology, function, and behavior is presented with the associated benefits and limitations. Ultimately, the necessity to assess and investigate renal disease based on in vivo readouts with a resolution up to capillary level may provide a paradigm shift for diagnosis and therapy in the field of nephrology.

scholarly journals Role of TGF-alpha in the progression of diabetic kidney disease

2017 ◽  
Vol 312 (6) ◽  
pp. F951-F962 ◽  
Author(s):  
Josef G. Heuer ◽  
Shannon M. Harlan ◽  
Derek D. Yang ◽  
Dianna L. Jaqua ◽  
Jeffrey S. Boyles ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Renal Disease ◽  
Neutralizing Antibodies ◽  
Diabetic Kidney Disease ◽  
Transforming Growth Factor ◽  
Renin Angiotensin System ◽  
Neutralizing Antibody ◽  
Diabetic Kidney

Transforming growth factor-alpha (TGFA) has been shown to play a role in experimental chronic kidney disease associated with nephron reduction, while its role in diabetic kidney disease (DKD) is unknown. We show here that intrarenal TGFA mRNA expression, as well as urine and serum TGFA, are increased in human DKD. We used a TGFA neutralizing antibody to determine the role of TGFA in two models of renal disease, the remnant surgical reduction model and the uninephrectomized (uniNx) db/db DKD model. In addition, the contribution of TGFA to DKD progression was examined using an adeno-associated virus approach to increase circulating TGFA in experimental DKD. In vivo blockade of TGFA attenuated kidney disease progression in both nondiabetic 129S6 nephron reduction and Type 2 diabetic uniNx db/db models, whereas overexpression of TGFA in uniNx db/db model accelerated renal disease. Therapeutic activity of the TGFA antibody was enhanced with renin angiotensin system inhibition with further improvement in renal parameters. These findings suggest a pathologic contribution of TGFA in DKD and support the possibility that therapeutic administration of neutralizing antibodies could provide a novel treatment for the disease.

scholarly journals Neutrophil Reverse Migration Becomes Transparent with Zebrafish

2012 ◽  
Vol 2012 ◽  
pp. 1-11 ◽  
Author(s):  
Taylor W. Starnes ◽  
Anna Huttenlocher
Keyword(s):  
Immune Responses ◽  
Current Knowledge ◽  
Imaging Techniques ◽  
The Novel ◽  
Imaging Studies ◽  
Advanced Imaging ◽  
Precise Control ◽  
Reverse Migration ◽  
A Site

The precise control of neutrophil-mediated inflammation is critical for both host defense and the prevention of immunopathology. In vivo imaging studies in zebrafish, and more recently in mice, have made the novel observation that neutrophils leave a site of inflammation through a process called neutrophil reverse migration. The application of advanced imaging techniques to the genetically tractable, optically transparent zebrafish larvae was critical for these advances. Still, the mechanisms underlying neutrophil reverse migration and its effects on the resolution or priming of immune responses remain unclear. Here, we review the current knowledge of neutrophil reverse migration, its potential roles in host immunity, and the live imaging tools that make zebrafish a valuable model for increasing our knowledge of neutrophil behavior in vivo.

scholarly journals Determinants of epithelial differentiation during early nephrogenesis.

1990 ◽  
Vol 1 (2) ◽  
pp. 127-139
Author(s):  
B M Brenner
Keyword(s):  
Kidney Disease ◽  
Renal Disease ◽  
Current Knowledge ◽  
Common Elements ◽  
Polycystic Kidney ◽  
Differentiation Markers ◽  
Rapid Sequence ◽  
New Knowledge ◽  
Organ Specific ◽  
Differentiation Marker

Organogenesis from undifferentiated progenitor cells and initiation of a society's new journal are developmental processes which share common elements. Both initially require a potent inducing stimulus followed in relatively rapid sequence by the appearance of organ-specific differentiation markers. These events are prerequisites to subsequent proliferation and maturation. Insofar as many postnatal forms of renal disease (e.g., hereditary glomerulopathies, infantile and adult forms of polycystic kidney disease, congenital dysplasias) owe their origins ultimately to disordered nephrogenesis, it is my belief that research in this area of nephrology should expand. It is further hoped that JASN will adopt this particular differentiation marker and serve as a forum for reporting the much-needed new knowledge to be gained. To "induce" the Journal's activity in this area I have summarized current knowledge and suggest directions in need of further investigation.

scholarly journals Mesenchymal Stem Cell-Based Therapy for Kidney Disease: A Review of Clinical Evidence

2016 ◽  
Vol 2016 ◽  
pp. 1-22 ◽  
Author(s):  
Anna Julie Peired ◽  
Alessandro Sisti ◽  
Paola Romagnani
Keyword(s):  
Clinical Trials ◽  
Kidney Disease ◽  
Lupus Erythematosus ◽  
Current Knowledge ◽  
Kidney Diseases ◽  
Kidney Injury ◽  
Human Kidney ◽  
Consensus Protocol ◽  
Paracrine Factors ◽  
Cell Based Therapy

Mesenchymal stem cells form a population of self-renewing, multipotent cells that can be isolated from several tissues. Multiple preclinical studies have demonstrated that the administration of exogenous MSC could prevent renal injury and could promote renal recovery through a series of complex mechanisms, in particular via immunomodulation of the immune system and release of paracrine factors and microvesicles. Due to their therapeutic potentials, MSC are being evaluated as a possible player in treatment of human kidney disease, and an increasing number of clinical trials to assess the safety, feasibility, and efficacy of MSC-based therapy in various kidney diseases have been proposed. In the present review, we will summarize the current knowledge on MSC infusion to treat acute kidney injury, chronic kidney disease, diabetic nephropathy, focal segmental glomerulosclerosis, systemic lupus erythematosus, and kidney transplantation. The data obtained from these clinical trials will provide further insight into safety, feasibility, and efficacy of MSC-based therapy in renal pathologies and allow the design of consensus protocol for clinical purpose.

scholarly journals Impact of strawberries on human health: insight into marginally discussed bioactive compounds for the Mediterranean diet

2009 ◽  
Vol 12 (9A) ◽  
pp. 1656-1662 ◽  
Author(s):  
Sara Tulipani ◽  
Bruno Mezzetti ◽  
Maurizio Battino
Keyword(s):  
Human Health ◽  
Current Knowledge ◽  
Potential Health ◽  
Folate Status ◽  
Health Promoting ◽  
Plasma Urate ◽  
Potential Impact ◽  
The Moment ◽  
The Impact

AbstractObjectiveTo review and update the current knowledge on the potential impact of strawberry on human health, with particular attention on compounds and indirect mechanisms of action not exhaustively considered.DesignPersonal perspectives and recent data.SettingInternational.ResultsOur research group was among the few groups that have recently investigated the folate content in fresh, stored and processed strawberries, and the data look very promising. As well, some in vivo evidence of the impact of strawberry intake on the folate status in humans have already been reported, but a new increasing interest on this field is strongly hoped. Furthermore, the hypouricaemic effects previously ascribed to cherry consumption need to be evaluated in respect to strawberry intake. At the moment, inconsistent results come from the few investigations designed at this proposal. In our studies, a great interindividual variability was observed on plasma urate levels in response to strawberry intake, suggesting a putative effect.ConclusionsThe mechanisms responsible for the potential health-promoting effects of strawberry may not be necessarily searched in the activity of phytochemicals. Particularly, a greater interest should be addressed to show whether a prolonged strawberry consumption may effectively improve the folate status and reduce the incidence of folate-related pathological conditions. Furthermore, the hypouricaemic effects of cherries need to be evaluated also in respect to strawberry intake, and the mechanisms of actions and anti-gout potentialities need to be studied in detail.Future investigations involving human trials should be aimed at following these underestimated scientific tracks.

scholarly journals Carbamylated Proteins in Renal Disease: Aggravating Factors or Just Biomarkers?

2022 ◽  
Vol 23 (1) ◽  
pp. 574
Author(s):  
Laëtitia Gorisse ◽  
Stéphane Jaisson ◽  
Christine Piétrement ◽  
Philippe Gillery
Keyword(s):  
Kidney Disease ◽  
Renal Disease ◽  
Protein Structures ◽  
Post Translational Modification ◽  
Kidney Disease Progression ◽  
Metabolic Consequence ◽  
Stage Renal Disease ◽  
End Stage

Carbamylation is a nonenzymatic post-translational modification resulting from the reaction between cyanate, a urea by-product, and proteins. In vivo and in vitro studies have demonstrated that carbamylation modifies protein structures and functions, triggering unfavourable molecular and cellular responses. An enhanced formation of carbamylation-derived products (CDPs) is observed in pathological contexts, especially during chronic kidney disease (CKD), because of increased blood urea. Significantly, studies have reported a positive correlation between serum CDPs and the evolutive state of renal failure. Further, serum concentrations of carbamylated proteins are characterized as strong predictors of mortality in end-stage renal disease patients. Over time, it is likely that these modified compounds become aggravating factors and promote long-term complications, including cardiovascular disorders and inflammation or immune system dysfunctions. These poor clinical outcomes have led researchers to consider strategies to prevent or slow down CDP formation. Even if growing evidence suggests the involvement of carbamylation in the pathophysiology of CKD, the real relevance of carbamylation is still unclear: is it a causal phenomenon, a metabolic consequence or just a biological feature? In this review, we discuss how carbamylation, a consequence of renal function decline, may become a causal phenomenon of kidney disease progression and how CDPs may be used as biomarkers.

scholarly journals Advances in Molecular Imaging Strategies forIn VivoTracking of Immune Cells

2016 ◽  
Vol 2016 ◽  
pp. 1-10 ◽  
Author(s):  
Ho Won Lee ◽  
Prakash Gangadaran ◽  
Senthilkumar Kalimuthu ◽  
Byeong-Cheol Ahn
Keyword(s):  
Computerized Tomography ◽  
Immune Cells ◽  
Cell Tracking ◽  
Immune Cell ◽  
Single Photon ◽  
Imaging Techniques ◽  
Photon Emission ◽  
Nuclear Imaging ◽  
Cell Based Therapy

Tracking of immune cellsin vivois a crucial tool for development and optimization of cell-based therapy. Techniques for tracking immune cells have been applied widely for understanding the intrinsic behavior of immune cells and include non-radiation-based techniques such as optical imaging and magnetic resonance imaging (MRI), radiation-based techniques such as computerized tomography (CT), and nuclear imaging including single photon emission computerized tomography (SPECT) and positron emission tomography (PET). Each modality has its own strengths and limitations. To overcome the limitations of each modality, multimodal imaging techniques involving two or more imaging modalities are actively applied. Multimodal techniques allow integration of the strengths of individual modalities. In this review, we discuss the strengths and limitations of currently available preclinicalin vivoimmune cell tracking techniques and summarize the value of immune cell tracking in the development and optimization of immune cell therapy for various diseases.

scholarly journals The Locus Coeruleus in Aging and Alzheimer’s Disease: A Postmortem and Brain Imaging Review

2021 ◽  
pp. 1-18
Author(s):  
Rebecca Beardmore ◽  
Ruihua Hou ◽  
Angela Darekar ◽  
Clive Holmes ◽  
Delphine Boche
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Locus Coeruleus ◽  
Current Knowledge ◽  
Imaging Techniques ◽  
Experimental Studies ◽  
Disease Process ◽  
Neuronal Loss

The locus coeruleus (LC), a tiny nucleus in the brainstem and the principal site of noradrenaline synthesis, has a major role in regulating autonomic function, arousal, attention, and neuroinflammation. LC dysfunction has been linked to a range of disorders; however particular interest is given to the role it plays in Alzheimer’s disease (AD). The LC undergoes significant neuronal loss in AD, thought to occur early in the disease process. While neuronal loss in the LC has also been suggested to occur in aging, this relationship is less clear as the findings have been contradictory. LC density has been suggested to be indicative of cognitive reserve and the evidence for these claims will be discussed. Recent imaging techniques allowing visualization of the LC in vivo using neuromelanin-sensitive MRI are developing our understanding of the role of LC in aging and AD. Tau pathology within the LC is evident at an early age in most individuals; however, the relationship between tau accumulation and neuronal loss and why some individuals then develop AD is not understood. Neuromelanin pigment accumulates within LC cells with age and is proposed to be toxic and inflammatory when released into the extracellular environment. This review will explore our current knowledge of the LC changes in both aging and AD from postmortem, imaging, and experimental studies. We will discuss the reasons behind the susceptibility of the LC to neuronal loss, with a focus on the role of extracellular neuromelanin and neuroinflammation caused by the dysfunction of the LC-noradrenaline pathway.

scholarly journals Biodistribution of Exosomes and Engineering Strategies for Targeted Delivery of Therapeutic Exosomes

2021 ◽  
Author(s):  
Hojun Choi ◽  
Yoorim Choi ◽  
Hwa Young Yim ◽  
Amin Mirzaaghasi ◽  
Jae-Kwang Yoo ◽  
...  
Keyword(s):  
Targeted Delivery ◽  
Surface Engineering ◽  
Therapeutic Potential ◽  
Current Knowledge ◽  
Imaging Techniques ◽  
Protein Composition ◽  
Covalent Bonds ◽  
Systemic Injection ◽  
Recent Advances

AbstractExosomes are cell-secreted nano-sized vesicles which deliver diverse biological molecules for intercellular communication. Due to their therapeutic potential, exosomes have been engineered in numerous ways for efficient delivery of active pharmaceutical ingredients to various target organs, tissues, and cells. In vivo administered exosomes are normally delivered to the liver, spleen, kidney, lung, and gastrointestinal tract and show rapid clearance from the blood circulation after systemic injection. The biodistribution and pharmacokinetics (PK) of exosomes can be modulated by engineering various factors such as cellular origin and membrane protein composition of exosomes. Recent advances accentuate the potential of targeted delivery of engineered exosomes even to the most challenging organs including the central nervous system. Major breakthroughs have been made related to various imaging techniques for monitoring in vivo biodistribution and PK of exosomes, as well as exosomal surface engineering technologies for inducing targetability. For inducing targeted delivery, therapeutic exosomes can be engineered to express various targeting moieties via direct modification methods such as chemically modifying exosomal surfaces with covalent/non-covalent bonds, or via indirect modification methods by genetically engineering exosome-producing cells. In this review, we describe the current knowledge of biodistribution and PK of exosomes, factors determining the targetability and organotropism of exosomes, and imaging technologies to monitor in vivo administered exosomes. In addition, we highlight recent advances in strategies for inducing targeted delivery of exosomes to specific organs and cells.

scholarly journals New Targets for End-Stage Chronic Kidney Disease Therapy

2015 ◽  
Vol 1 (3) ◽  
pp. 92-95 ◽  
Author(s):  
Niki Prakoura ◽  
Panos Kavvadas ◽  
Christos Chatziantoniou
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Renal Disease ◽  
Matrix Protein ◽  
Tooth Development ◽  
Membrane Receptors ◽  
Extracellular Matrix Protein ◽  
Renal Vascular Disease ◽  
End Stage

Abstract Severe forms of chronic kidney disease can lead to a critical, end-stage condition, requiring renal replacement therapy, which may involve a form of dialysis or renal transplantation. Identification and characterization of novel markers and/or targets of therapy that could be applied in these critically ill patients remains the focus of the current research in the field of critical care medicine and has been the objective of our studies for some years past. To this end, we used models of renal vascular disease, Ang II, L-NAME or mice overexpressing renin, treated with AT1 antagonists at different stages of progression, to create cohorts of animals during progression, reversal or escape from therapy. Transcriptomic analysis and comparisons were performed and genes were selected according to the following criteria: a) not previously described in the kidney, b) highly upregulated during progression and returning to the normal levels during reversal, and c) producing proteins that are either circulating or membrane receptors. The involvement of the selected genes in the mechanisms of renal disease was confirmed in additional models of renal disease, initiated in other compartments of the kidney such as glomeruli (administration of nephrotoxic serum) or the tubular interstitium (unilateral ureteral obstruction). The potential of the therapy was tested using mice lacking the expression of these genes and by in vivo administration of antisense oligonucleotides which blocked the transcription of the targeted genes. This strategy allowed the identification of periostin, an extracellular matrix protein normally involved in bone and tooth development, in addition to the discoidin domain receptor1 (DDR1) as potential targets of therapy against renal inflammation and fibrosis.

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