scholarly journals Human Urine as a Noninvasive Source of Kidney Cells

2015 ◽  
Vol 2015 ◽  
pp. 1-7 ◽  
Author(s):  
Fanny Oliveira Arcolino ◽  
Agnès Tort Piella ◽  
Elli Papadimitriou ◽  
Benedetta Bussolati ◽  
Daniel J. Antonie ◽  
...  
Keyword(s):  
Ethical Issues ◽  
Kidney Injury ◽  
Human Kidney ◽  
Patient Specific ◽  
Kidney Cells ◽  
Proximal Tubule Cells ◽  
Disease Mechanisms ◽  
Viable Cells ◽  
Novel Drug

Urine represents an unlimited source of patient-specific kidney cells that can be harvested noninvasively. Urine derived podocytes and proximal tubule cells have been used to study disease mechanisms and to screen for novel drug therapies in a variety of human kidney disorders. The urinary kidney stem/progenitor cells and extracellular vesicles, instead, might be promising for therapeutic treatments of kidney injury. The greatest advantages of urine as a source of viable cells are the easy collection and less complicated ethical issues. However, extensive characterization andin vivostudies still have to be performed before the clinical use of urine-derived kidney progenitors.

scholarly journals Kidney Organoids as a Novel Platform to Evaluate Lipopolysaccharide-Induced Oxidative Stress and Apoptosis in Acute Kidney Injury

2021 ◽  
Vol 8 ◽  
Author(s):  
Weitao Zhang ◽  
Ruochen Qi ◽  
Tingting Li ◽  
Xuepeng Zhang ◽  
Yi Shi ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Acute Kidney Injury ◽  
Immune Cell ◽  
Kidney Injury ◽  
Human Kidney ◽  
Kidney Cells ◽  
Pathological Changes ◽  
Kidney Organoids

Sepsis-associated acute kidney injury (SA-AKI) is a life-threatening syndrome. Lipopolysaccharide (LPS) is a widely used inducer for modeling SA-AKI both in vivo and in vitro. However, due to the innate complexity of the kidney architecture, the mechanisms underlying the pathogenesis of SA-AKI, as well as those involved in LPS-induced kidney injury remain to be clarified. Kidney organoids derived from human pluripotent stem cells (hPSCs) act as a model of multiple types of kidney cells in vitro and eliminate potential confounders in vivo. In the current study, we established LPS-induced kidney injury models both in vivo and in human kidney organoids. Kidney function, pathological changes, and markers of oxidative stress were evaluated with/without the presence of methylprednisolone (MP) treatment both in vivo and in vitro. The extent of LPS-induced oxidative stress and apoptosis in kidney organoids was further investigated in vitro. LPS-induced acute kidney injury in mice, together with pathological changes and increased oxidative stress, as well as enhanced apoptosis in kidney cells were evaluated. These phenomena were ameliorated by MP treatment. Experiments in kidney organoids showed that the LPS-induced apoptotic effects occurred mainly in podocytes and proximal tubular cells. Our experiments demonstrated the efficacy of using kidney organoids as a solid platform to study LPS-induced kidney injury. LPS induced oxidative stress as well as apoptosis in kidney cells independently of changes in perfusion or immune cell infiltration. MP treatment partially alleviated LPS-induced injury by reducing kidney cell oxidative stress and apoptosis.

scholarly journals IN VIVO AND IN VITRO EXPRESSION OF SOMATOSTATIN BY HUMAN KIDNEY CELLS. • 2213

1996 ◽  
Vol 39 ◽  
pp. 371-371
Author(s):  
Martin A Turman ◽  
M. Sue O'Dorisio ◽  
Thomas M O'Dorisio ◽  
Courtney A Apple
Keyword(s):  
Human Kidney ◽  
Kidney Cells ◽  
In Vitro Expression

scholarly journals Silencing Long Non-coding RNA Kcnq1ot1 Limits Acute Kidney Injury by Promoting miR-204-5p and Blocking the Activation of NLRP3 Inflammasome

2021 ◽  
Vol 12 ◽  
Author(s):  
JunTao Wang ◽  
Peng Jiao ◽  
XiaoYing Wei ◽  
Yun Zhou
Keyword(s):  
Cell Proliferation ◽  
Acute Kidney Injury ◽  
Nlrp3 Inflammasome ◽  
Kidney Injury ◽  
Human Kidney ◽  
Inflammasome Activation ◽  
Nlrp3 Inflammasome Activation ◽  
Apoptosis And Inflammation

Acute kidney injury (AKI) is a critical clinical disease characterized by an acute decrease in renal function. Long non-coding RNAs (LncRNAs) are important in AKI. This study aimed to explore the mechanism of lncRNA Kcnq1ot1 in AKI by sponging microRNA (miR)-204-5p as a competitive endogenous RNA (ceRNA). AKI mouse model and hypoxia/reoxygenation (H/R) model of human kidney (HK) cells were established. Kcnq1ot1 expression, cell proliferation, and apoptosis were measured. Binding relations among Kcnq1ot1, miR-204-5p, and NLRP3 were verified. Pathological changes and cell apoptosis were detected. The results showed that Kcnq1ot1 was highly expressed in the AKI model in vivo and in vitro. Kcnq1ot1 knockdown promoted cell proliferation and prevented apoptosis and inflammation. Furthermore, Kcnq1ot1 inhibited miR-204-5p expression by competitively binding to miR-204-5p in HK-2 cells. miR-204-5p targeted NLRP3 and NLRP3 overexpression averted the inhibiting effect of miR-204-5p on apoptosis and inflammation in HK-2 cells in vitro. Kcnq1ot1 knockdown in vivo promoted miR-204-5p expression, inhibited NLRP3 inflammasome activation, reduced levels of SCr, BUN, and KIM-1, and thus alleviated AKI and reduced apoptosis. In summary, silencing lncRNA Kcnq1ot1 inhibited AKI by promoting miR-204-5p and inhibiting NLRP3 inflammasome activation.

scholarly journals Interleukin-1β Activates a MYC-Dependent Metabolic Switch in Kidney Stromal Cells Necessary for Progressive Tubulointerstitial Fibrosis

2018 ◽  
Vol 29 (6) ◽  
pp. 1690-1705 ◽  
Author(s):  
Dario R. Lemos ◽  
Michael McMurdo ◽  
Gamze Karaca ◽  
Julia Wilflingseder ◽  
Irina A. Leaf ◽  
...  
Keyword(s):  
Stromal Cells ◽  
Target Genes ◽  
Kidney Injury ◽  
Human Kidney ◽  
Metabolic Switch ◽  
Metabolic Derangement ◽  
Sequestosome 1 ◽  
Kidney Organoids

Background Kidney injury is characterized by persisting inflammation and fibrosis, yet mechanisms by which inflammatory signals drive fibrogenesis remain poorly defined.Methods RNA sequencing of fibrotic kidneys from patients with CKD identified a metabolic gene signature comprising loss of mitochondrial and oxidative phosphorylation gene expression with a concomitant increase in regulators and enzymes of glycolysis under the control of PGC1α and MYC transcription factors, respectively. We modeled this metabolic switch in vivo, in experimental murine models of kidney injury, and in vitro in human kidney stromal cells (SCs) and human kidney organoids.Results In mice, MYC and the target genes thereof became activated in resident SCs early after kidney injury, suggesting that acute innate immune signals regulate this transcriptional switch. In vitro, stimulation of purified human kidney SCs and human kidney organoids with IL-1β recapitulated the molecular events observed in vivo, inducing functional metabolic derangement characterized by increased MYC-dependent glycolysis, the latter proving necessary to drive proliferation and matrix production. MYC interacted directly with sequestosome 1/p62, which is involved in proteasomal degradation, and modulation of p62 expression caused inverse effects on MYC expression. IL-1β stimulated autophagy flux, causing degradation of p62 and accumulation of MYC. Inhibition of the IL-1R signal transducer kinase IRAK4 in vivo or inhibition of MYC in vivo as well as in human kidney organoids in vitro abrogated fibrosis and reduced tubular injury.Conclusions Our findings define a connection between IL-1β and metabolic switch in fibrosis initiation and progression and highlight IL-1β and MYC as potential therapeutic targets in tubulointerstitial diseases.

scholarly journals A tissue-bioengineering strategy for modeling rare human kidney diseases in vivo

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
J. O. R. Hernandez ◽  
X. Wang ◽  
M. Vazquez-Segoviano ◽  
M. Lopez-Marfil ◽  
M. F. Sobral-Reyes ◽  
...  
Keyword(s):  
Kidney Diseases ◽  
Human Kidney ◽  
Cell Phenotype ◽  
Transcriptional Signature ◽  
Disease Mechanisms ◽  
Genetic Mechanisms ◽  
Experimental Approaches ◽  
Kidney Lesions ◽  
Kidney Organoids

AbstractThe lack of animal models for some human diseases precludes our understanding of disease mechanisms and our ability to test prospective therapies in vivo. Generation of kidney organoids from Tuberous Sclerosis Complex (TSC) patient-derived-hiPSCs allows us to recapitulate a rare kidney tumor called angiomyolipoma (AML). Organoids derived from TSC2−/− hiPSCs but not from isogenic TSC2+/− or TSC2+/+ hiPSCs share a common transcriptional signature and a myomelanocytic cell phenotype with kidney AMLs, and develop epithelial cysts, replicating two major TSC-associated kidney lesions driven by genetic mechanisms that cannot be consistently recapitulated with transgenic mice. Transplantation of multiple TSC2−/− renal organoids into the kidneys of immunodeficient rats allows us to model AML in vivo for the study of tumor mechanisms, and to test the efficacy of rapamycin-loaded nanoparticles as an approach to rapidly ablate AMLs. Collectively, our experimental approaches represent an innovative and scalable tissue-bioengineering strategy for modeling rare kidney disease in vivo.

scholarly journals A rapid in vivo assay system for analyzing the organogenetic capacity of human kidney cells

Organogenesis ◽  
2011 ◽  
Vol 7 (2) ◽  
pp. 140-144 ◽  
Author(s):  
Tsahi Noiman ◽  
Ella Buzhor ◽  
Sally Metsuyanim ◽  
Orit Harari-Steinberg ◽  
Chaya Morgenshtern ◽  
...  
Keyword(s):  
Human Kidney ◽  
Assay System ◽  
Kidney Cells ◽  
In Vivo Assay

scholarly journals Parallel generation of extensive vascular networks with application to an archetypal human kidney model

2021 ◽  
Vol 8 (12) ◽  
Author(s):  
L. F. M. Cury ◽  
G. D. Maso Talou ◽  
M. Younes-Ibrahim ◽  
P. J. Blanco
Keyword(s):  
Computer Simulation ◽  
Complex Geometry ◽  
Human Kidney ◽  
Automatic Generation ◽  
Level Of Detail ◽  
Patient Specific ◽  
Vascular Networks ◽  
Organ Function ◽  
Network Update

Given the relevance of the inextricable coupling between microcirculation and physiology, and the relation to organ function and disease progression, the construction of synthetic vascular networks for mathematical modelling and computer simulation is becoming an increasingly broad field of research. Building vascular networks that mimic in vivo morphometry is feasible through algorithms such as constrained constructive optimization (CCO) and variations. Nevertheless, these methods are limited by the maximum number of vessels to be generated due to the whole network update required at each vessel addition. In this work, we propose a CCO-based approach endowed with a domain decomposition strategy to concurrently create vascular networks. The performance of this approach is evaluated by analysing the agreement with the sequentially generated networks and studying the scalability when building vascular networks up to 200 000 vascular segments. Finally, we apply our method to vascularize a highly complex geometry corresponding to the cortex of a prototypical human kidney. The technique presented in this work enables the automatic generation of extensive vascular networks, removing the limitation from previous works. Thus, we can extend vascular networks (e.g. obtained from medical images) to pre-arteriolar level, yielding patient-specific whole-organ vascular models with an unprecedented level of detail.

scholarly journals Modeling oxidative injury response in human kidney organoids

2021 ◽  
Author(s):  
Aneta Przepiorski ◽  
Thitinee Vanichapol ◽  
Eugenel B. Espiritu ◽  
Amanda E. Crunk ◽  
Emily Parasky ◽  
...  
Keyword(s):  
Ischemia Reperfusion ◽  
Organic Anion ◽  
Kidney Injury ◽  
Induced Pluripotent Stem Cell ◽  
Human Kidney ◽  
Mitochondrial Morphology ◽  
Tubular Atrophy ◽  
Kidney Fibrosis ◽  
Kidney Organoids

Abstract BackgroundPersistent acute kidney injury (AKI) leads to tubular atrophy, kidney fibrosis, and, if severe enough, chronic kidney disease (CKD). A common feature of AKI is the generation of excessive reactive oxygen species (ROS) which damage cells and induce inflammation. MethodsHuman kidney organoids were treated with hemin, an iron-containing porphyrin derived from lysed red blood cells, that generates ROS in disease settings such as rhabdomyolysis, sepsis and ischemia reperfusion leading to AKI. In addition, we developed an induced pluripotent stem cell line expressing the biosensor, CytochromeC-GFP (CytoC-GFP), which provides a real-time readout of mitochondrial morphology, health, and early apoptotic events. ResultsWe found that hemin-treated kidney organoids show oxidative damage, increased expression of injury markers, impaired functionality of organic anion and cation transport and undergo fibrosis. Tubule injury could be detected in live CytoC-GFP organoids by cytoplasmic localization of fluorescence. Finally, we show that 4-(phenylthio)butanoic acid, an HDAC inhibitor with anti-fibrotic effects in vivo , reduces hemin-induced human kidney organoid fibrosis. ConclusionTogether this work establishes a hemin-induced model of kidney organoid injury and fibrosis as a new model to study renal repair and a human platform for developing AKI therapeutics.

scholarly journals SIRT1-mediated HMGB1 deacetylation suppresses sepsis-associated acute kidney injury

2019 ◽  
Vol 316 (1) ◽  
pp. F20-F31 ◽  
Author(s):  
Siwei Wei ◽  
Youguang Gao ◽  
Xingui Dai ◽  
Weijun Fu ◽  
Shumin Cai ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Posttranslational Modifications ◽  
Cecal Ligation ◽  
High Mobility ◽  
Kidney Injury ◽  
Human Kidney ◽  
Sirtuin 1 ◽  
Kidney Cells ◽  
Extracellular Secretion ◽  
Related Enzyme

Sepsis is the leading cause of death in the intensive care unit and continues to lack effective treatment. It is widely accepted that high-mobility group box 1 (HMGB1) is a key inflammatory mediator in the pathogenesis of sepsis. Moreover, some studies indicate that the functions of HMGB1 depend on its molecular localization and posttranslational modifications. Our previous study confirms that sirtuin 1, silent information regulator 2-related enzyme 1 (SIRT1), a type III deacetylase, can ameliorate sepsis-associated acute kidney injury (SA-AKI). We explored the effect and mechanism of SIRT1 on HMGB1 using a mouse model of cecal ligation and puncture-induced sepsis and LPS-treated human kidney (HK-2) cell line. We found that HMGB1 is elevated in the serum but is gradually reduced in kidney cells in the later stages of septic mice. The acetylation modification of HMGB1 is a key process before its nucleus-to-cytoplasm translocation and extracellular secretion in kidney cells, accelerating the development of SA-AKI. Moreover, SIRT1 can physically interact with HMGB1 at the deacetylated lysine sites K28, K29, and K30, subsequently suppressing downstream inflammatory signaling. Thus the SIRT1-HMGB1 signaling pathway is a crucial mechanism in the development of SA-AKI and presents a novel experimental perspective for future SA-AKI research.

scholarly journals Maintenance of vascular integrity by pericytes is essential for normal kidney function

2016 ◽  
Vol 311 (6) ◽  
pp. F1230-F1242 ◽  
Author(s):  
Dario R. Lemos ◽  
Graham Marsh ◽  
Angela Huang ◽  
Gabriela Campanholle ◽  
Takahide Aburatani ◽  
...  
Keyword(s):  
Basement Membrane ◽  
Vascular Function ◽  
Kidney Injury ◽  
Enrichment Analysis ◽  
Human Kidney ◽  
Cell Swelling ◽  
Pathway Enrichment Analysis ◽  
Mesenchymal Progenitor Cells ◽  
Peritubular Capillaries

Pericytes are tissue-resident mesenchymal progenitor cells anatomically associated with the vasculature that have been shown to participate in tissue regeneration. Here, we tested the hypothesis that kidney pericytes, derived from FoxD1+ mesodermal progenitors during embryogenesis, are necessary for postnatal kidney homeostasis. Diphtheria toxin delivery to FoxD1Cre::RsDTR transgenic mice resulted in selective ablation of >90% of kidney pericytes but not other cell lineages. Abrupt increases in plasma creatinine, blood urea nitrogen, and albuminuria within 96 h indicated acute kidney injury in pericyte-ablated mice. Loss of pericytes led to a rapid accumulation of neutral lipid vacuoles, swollen mitochondria, and apoptosis in tubular epithelial cells. Pericyte ablation led to endothelial cell swelling, reduced expression of vascular homeostasis markers, and peritubular capillary loss. Despite the observed injury, no signs of the acute inflammatory response were observed. Pathway enrichment analysis of genes expressed in kidney pericytes in vivo identified basement membrane proteins, angiogenic factors, and factors regulating vascular tone as major regulators of vascular function. Using novel microphysiological devices, we recapitulated human kidney peritubular capillaries coated with pericytes and showed that pericytes regulate permeability, basement membrane deposition, and microvascular tone. These findings suggest that through the active support of the microvasculature, pericytes are essential to adult kidney homeostasis.

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