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https://www.readbyqxmd.com/read/29055226/generation-of-an-induced-pluripotent-stem-cell-line-ibms-ipsc-014-05-from-a-female-autosomal-dominant-polycystic-kidney-disease-patient-carrying-a-common-mutation-of-r803x-in-pkd2
#1
Ming-Ching Ho, Ching-Ying Huang, Jia-Jung Lee, Shih-Han Hsu, Yu-Che Cheng, Yu-Hung Hsu, Daw-Yang Hwang, Huai-En Lu, Hung-Chun Chen, Patrick C H Hsieh
Autosomal dominant polycystic kidney disease (ADPKD) is one of the most commonly inherited forms of polycystic kidney disease, and is characterized by the growth of numerous cysts in both kidneys. Here we generated an induced pluripotent stem cell (iPSC) line from the peripheral blood mononuclear cells (PBMCs) of a 63-year-old female ADPKD patient carrying an R803X mutation in the PKD2 gene using the Sendai-virus delivery system. Downstream characterization of these iPSCs showed that they possessed normal karyotyping, were free of genomic integration, retained the disease-causing PKD2 mutation, expressed pluripotency markers and could differentiate into three germ layers...
October 10, 2017: Stem Cell Research
https://www.readbyqxmd.com/read/29054531/the-ammonia-transporter-rhcg-modulates-urinary-acidification-by-interacting-with-the-vacuolar-proton-atpases-in-renal-intercalated-cells
#2
Soline Bourgeois, Lisa Bounoure, Isabelle Mouro-Chanteloup, Yves Colin, Dennis Brown, Carsten A Wagner
Ammonium, stemming from renal ammoniagenesis, is a major urinary proton buffer and is excreted along the collecting duct. This process depends on the concomitant secretion of ammonia by the ammonia channel RhCG and of protons by the vacuolar-type proton-ATPase pump. Thus, urinary ammonium content and urinary acidification are tightly linked. However, mice lacking Rhcg excrete more alkaline urine despite lower urinary ammonium, suggesting an unexpected role of Rhcg in urinary acidification. RhCG and the B1 and B2 proton-ATPase subunits could be co-immunoprecipitated from kidney...
October 17, 2017: Kidney International
https://www.readbyqxmd.com/read/29050313/adipose-derived-mesenchymal-stem-cells-employed-exosomes-to-attenuate-aki-ckd-transition-through-tubular-epithelial-cell-dependent-sox9-activation
#3
Fengming Zhu, Octavia L S Chong Lee Shin, Guangchang Pei, Zhizhi Hu, Juan Yang, Han Zhu, Meng Wang, Jingyi Mou, Jie Sun, Yuxi Wang, Qian Yang, Zhi Zhao, Huzi Xu, Hui Gao, Weiqi Yao, Xiao Luo, Wenhui Liao, Gang Xu, Rui Zeng, Ying Yao
Acute kidney injury (AKI) predisposes patients to an increased risk into progressive chronic kidney disease (CKD), however effective treatments are still elusive. This study aimed to investigate the therapeutic efficacy of human adipose-derived MSCs (hAD-MSCs) in the prevention of AKI-CKD transition, and illuminate the role of Sox9, a vital transcription factor in the development of kidney, in this process. C57BL/6 mice were subjected to unilateral renal ischemia/reperfusion (I/R) with or without hAD-MSC treatment...
September 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29050031/reading-first-coordinates-from-the%C3%A2-nephrogenic-zone-in-human-fetal%C3%A2-kidney
#4
Will W Minuth
While substantial information is available on organ anlage and the primary formation of nephrons, molecular mechanisms acting during the late development of the human kidney have received an astonishing lack of attention. In healthy newborn babies, nephrogenesis takes place unnoticed until birth. Upon delivery, morphogenetic activity in the nephrogenic zone decreases, and the stem cell niches aligned beyond the organ capsule vanish by an unknown signal. However, this signal also plays a key role in preterm and low birth weight babies...
October 19, 2017: Nephron
https://www.readbyqxmd.com/read/29043663/nephrotoxicity-induced-by-cisplatin-intake-in-experimental-rats-and-therapeutic-approach-of-using-mesenchymal-stem-cells-and-spironolactone
#5
Mohamed M Elseweidy, Mervat E Askar, Sahar E Elswefy, Mohamed Shawky
Chronic kidney disease may lead to subsequent tissue fibrosis. However, many factors can combat injurious stimuli in these tissues aiming to repair, heal, and alleviate any disturbance. Chemokines release, migration of inflammatory cells to the affected site, and activation of fibroblasts for the production of extracellular matrix are commonly observed in this disease. In the last years, many studies have focused on spironolactone (SPL), a mineralocorticoid receptor antagonist, and its pharmacological effects...
October 17, 2017: Applied Biochemistry and Biotechnology
https://www.readbyqxmd.com/read/29038743/mature-induced-pluripotent-stem-cell-derived-human-podocytes-reconstitute-kidney-glomerular-capillary-wall-function-on-a-chip
#6
Samira Musah, Akiko Mammoto, Thomas C Ferrante, Sauveur S F Jeanty, Mariko Hirano-Kobayashi, Tadanori Mammoto, Kristen Roberts, Seyoon Chung, Richard Novak, Miles Ingram, Tohid Fatanat-Didar, Sandeep Koshy, James C Weaver, George M Church, Donald E Ingber
An in vitro model of the human kidney glomerulus - the major site of blood filtration - could facilitate drug discovery and illuminate kidney-disease mechanisms. Microfluidic organ-on-a-chip technology has been used to model the human proximal tubule, yet a kidney-glomerulus-on-a-chip has not been possible because of the lack of functional human podocytes - the cells that regulate selective permeability in the glomerulus. Here, we demonstrate an efficient (> 90%) and chemically defined method for directing the differentiation of human induced pluripotent stem (hiPS) cells into podocytes that express markers of the mature phenotype (nephrin+, WT1+, podocin+, Pax2-) and that exhibit primary and secondary foot processes...
2017: Nature biomedical engineering
https://www.readbyqxmd.com/read/29038571/highly-sensitive-and-specific-alu-based-quantification-of-human-cells-among-rodent-cells
#7
Kodai Funakoshi, Mozhdeh Bagheri, Ming Zhou, Ryoji Suzuki, Hiroshi Abe, Hideo Akashi
Alu elements are primate-specific short interspersed elements (SINEs), over 1 million copies of which are present in the human genome; thus, Alu elements are useful targets for detecting human cells. However, previous Alu-based techniques for detecting human genomic DNA do not reach the theoretical limits of sensitivity and specificity. In this study, we developed a highly sensitive and specific Alu-based real-time PCR method for discriminating human cells from rodent cells, using a primer and probe set carefully designed to avoid possible cross-reactions with rodent genomes...
October 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29038286/allogeneic-mesenchymal-stem-cells-for-treatment-of-aki-after-cardiac-surgery
#8
Madhav Swaminathan, Mark Stafford-Smith, Glenn M Chertow, David G Warnock, Viken Paragamian, Robert M Brenner, François Lellouche, Alison Fox-Robichaud, Mohamed G Atta, Spencer Melby, Ravindra L Mehta, Ron Wald, Subodh Verma, C David Mazer
AKI after cardiac surgery remains strongly associated with mortality and lacks effective treatment or prevention. Preclinical studies suggest that cell-based interventions may influence functional recovery. We conducted a phase 2, randomized, double-blind, placebo-controlled trial in 27 centers across North America to determine the safety and efficacy of allogeneic human mesenchymal stem cells (MSCs) in reducing the time to recovery from AKI after cardiac surgery. We randomized 156 adult subjects undergoing cardiac surgery with evidence of early AKI to receive intra-aortic MSCs (AC607; n=67) or placebo (n=68)...
October 16, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/29037855/nephrosphere-derived-cells-are-induced-to-multilineage-differentiation-when-cultured-on-human-decellularized-kidney-scaffolds
#9
Silvia Bombelli, Chiara Meregalli, Carla Scalia, Giorgio Bovo, Barbara Torsello, Sofia De Marco, Massimiliano Cadamuro, Paolo Viganò, Guido Strada, Giorgio Cattoretti, Cristina Bianchi, Roberto A Perego
In end-stage chronic kidney disease, the option of organ transplantation is limited due to the scarce availability of kidneys. The combination of stem cell research, regenerative medicine, and tissue engineering seems a promising approach to produce new transplantable kidneys. Currently, the possibility to repopulate naturally obtained scaffolds with cells of different sources is advancing. Our aim was to test, for the first time, whether the nephrosphere (NS) cells, composed by renal stem/progenitor-like cells, were able to repopulate different nephron portions of renal extracellular matrix scaffolds obtained after decellularization of human renal tissue slices...
October 13, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/29034881/generation-of-induced-pluripotent-stem-cells-derived-from-an-autosomal-dominant-polycystic-kidney-disease-patient-with-a-p-ser1457fs-mutation-in-pkd1
#10
Ching-Ying Huang, Ming-Ching Ho, Jia-Jung Lee, Daw-Yang Hwang, Hui-Wen Ko, Yu-Che Cheng, Yu-Hung Hsu, Huai-En Lu, Hung-Chun Chen, Patrick C H Hsieh
Autosomal dominant polycystic kidney disease is one of the most prevalent forms of inherited cystic kidney disease, and can be characterized by kidney cyst formation and enlargement. Here we report the generation of a Type 1 ADPKD disease iPS cell line, IBMS-iPSC-012-12, which retains the conserved deletion of PKD1, normal karyotype and exhibits the properties of pluripotent stem cells such as ES-like morphology, expression of pluripotent markers and capacity to differentiate into all three germ layers. Our results show that we have successfully generated a patient-specific iPS cell line with a mutation in PKD1 for study of renal disease pathophysiology...
October 2017: Stem Cell Research
https://www.readbyqxmd.com/read/29033833/cell-based-therapies-for-tissue-fibrosis
#11
REVIEW
Rebecca Lim, Sharon D Ricardo, William Sievert
The development of tissue fibrosis in the context of a wound-healing response to injury is common to many chronic diseases. Unregulated or persistent fibrogenesis may lead to structural and functional changes in organs that increase the risk of significant morbidity and mortality. We will explore the natural history, epidemiology, and pathogenesis of fibrotic disease affecting the lungs, kidneys, and liver as dysfunction of these organs is responsible for a substantial proportion of global mortality. For many patients with end-stage disease, organ transplantation is the only effective therapy to prolong life...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29021306/characterization-of-a-human-induced-pluripotent-stem-cell-derived-cardiomyocyte-model-for-the-study-of-variant-pathogenicity-validation-of-a-kcnj2-mutation
#12
Roselle Gélinas, Nabil El Khoury, Marie-A Chaix, Claudine Beauchamp, Azadeh Alikashani, Nathalie Ethier, Gabrielle Boucher, Louis Villeneuve, Laura Robb, Frédéric Latour, Blandine Mondesert, Lena Rivard, Philippe Goyette, Mario Talajic, Céline Fiset, John David Rioux
BACKGROUND: Long-QT syndrome is a potentially fatal condition for which 30% of patients are without a genetically confirmed diagnosis. Rapid identification of causal mutations is thus a priority to avoid at-risk situations that can lead to fatal cardiac events. Massively parallel sequencing technologies are useful for the identification of sequence variants; however, electrophysiological testing of newly identified variants is crucial to demonstrate causality. Long-QT syndrome could, therefore, benefit from having a standardized platform for functional characterization of candidate variants in the physiological context of human cardiomyocytes...
October 2017: Circulation. Cardiovascular Genetics
https://www.readbyqxmd.com/read/28993399/myc-cooperates-with-beta-catenin-to-drive-gene-expression-in-the-nephron-progenitor-cells
#13
Xinchao Pan, Courtney M Karner, Thomas J Carroll
For organs to achieve their proper size, the processes of stem cell renewal and differentiation must be tightly regulated. We previously showed that in the developing kidney, Wnt9b regulates distinct beta-catenin-dependent transcriptional programs in the renewing and differentiating populations of the nephron progenitor cells. How beta-catenin stimulated these two distinct programs was unclear. Here, we show that beta-catenin cooperates with the transcription factor Myc to activate the progenitor renewal program...
October 9, 2017: Development
https://www.readbyqxmd.com/read/28992100/prenatal-exposure-to-lps-alters-the-intrarenal-ras-in-offspring-which-is-ameliorated-by-adipose-tissue-derived-mesenchymal-stem-cells
#14
Xian-Fei Ding, Mou Sun, Fang-Xia Guan, Li-Na Guo, Yan-Yan Zhang, You-Dong Wan, Xiao-Juan Zhang, Yan-Wu Yu, Shan-Shan Ma, Hai-Mu Yao, Rui Yao, Rui-Fang Zhang, Tong-Wen Sun, Quan-Cheng Kan
BACKGROUND: Prenatal lipopolysaccharide (LPS) exposure causes hypertension in rat offspring through an unknown mechanism. Here, we investigated the role of the intrarenal renin-angiotensin system (RAS) in hypertension induced by prenatal LPS exposure and also explored whether adipose tissue-derived mesenchymal stem cells (ADSCs) can ameliorate the effects of prenatal LPS exposure in rat offspring. METHODS: Sixty-four pregnant rats were randomly divided into 4 groups (n = 16 in each), namely, a control group and an LPS group, which were intraperitoneally injected with vehicle and 0...
July 15, 2017: American Journal of Hypertension
https://www.readbyqxmd.com/read/28990105/microrna%C3%A2-24%C3%A2-2-is-associated-with-cell-proliferation-invasion-migration-and-apoptosis-in-renal-cell-carcinoma
#15
Lu Jin, Yifan Li, Liping Nie, Tao He, Jia Hu, Jiaju Liu, Mingwei Chen, Min Shi, Zhimao Jiang, Yaoting Gui, Shangqi Yang, Yongqing Lai
Micro (mi)RNAs are involved in multiple cellular processes, and alterations in miRNA expression have been demonstrated to lead to tumorigenesis. Previous microarray analysis revealed that miRNA (miR)‑24 was downregulated in renal cell carcinoma (RCC). Additionally, miR‑24 has been identified as an oncogene and tumor suppressor in various cancers. The present study assessed the expression levels of two stem‑loops of miR‑24, miR‑24‑1 and miR‑24‑2, in RCC tissues and paired healthy tissues by reverse transcription‑quantitative polymerase chain reaction...
October 4, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28988229/studying-kidney-disease-using-tissue-and-genome-engineering-in-human-pluripotent-stem-cells
#16
Elena Garreta, Federico González, Núria Montserrat
Kidney morphogenesis and patterning have been extensively studied in animal models such as the mouse and zebrafish. These seminal studies have been key to define the molecular mechanisms underlying this complex multistep process. Based on this knowledge, the last 3 years have witnessed the development of a cohort of protocols allowing efficient differentiation of human pluripotent stem cells (hPSCs) towards defined kidney progenitor populations using two-dimensional (2D) culture systems or through generating organoids...
October 7, 2017: Nephron
https://www.readbyqxmd.com/read/28987247/impact-of-autologous-stem-cell-transplantation-on-blood-pressure-and-renal-function-in-multiple-myeloma-patients
#17
Leah Balsam, Chadi Saad, Camelia Arsene, Joshua Fogel
BACKGROUND: Autologous stem cell transplantation (ASCT) reverses kidney failure in one-third of multiple myeloma (MM) patients, which may lead to blood pressure (BP) improvement. We evaluate the long term impact of ASCT on BP and renal function in MM patients. METHODS: We studied 192 MM patients that underwent ASCT. We compared BP readings and glomerular filtration rate (GFR) at 4 weeks before ASCT, on day of ASCT and post-ASCT at 30, 100 and 180 days. RESULTS: Mean systolic blood pressure (SBP) and diastolic blood pressure (DBP) on day of ASCT and at both 30 and 100 days post-ASCT was significantly lower as compared to pre-ASCT SBP and DBP...
2017: Journal of the National Medical Association
https://www.readbyqxmd.com/read/28985199/renal-lineage-cells-as-a-source-for-renal-regeneration
#18
REVIEW
Oren Pleniceanu, Dorit Omer, Orit Harari-Steinberg, Benjamin Dekel
The mammalian kidney is a highly complex organ, composed of various cell types within a unique structural framework. Nonetheless, in recent years, giant leaps in our understanding of nephrogenesis and the origin of new cells in the adult kidney, have resulted in novel routes to regenerate damaged nephrons. While several strategies can be envisioned to achieve this aim, one common theme is the reliance on renal lineage cells, since extra-renal cells, such as bone-marrow derived cells, have been shown to be devoid of renal differentiation capacity...
October 6, 2017: Pediatric Research
https://www.readbyqxmd.com/read/28976282/injectable-co-gels-of-collagen-and-decellularized-vascular-matrix-improve-msc-based-therapy-for-acute-kidney-injury
#19
Shuang Huang, Yajian Li, Xinning Wang, Xin Ma, Xu Zhang
Transplantation of mesenchymal stem cells (MSCs) is promising for treatment of acute kidney injury (AKI), but their therapeutic effects are often limited under normal conditions. In this study, we prepared the co-gels of decellularized vascular matrix and collagen, and investigated whether the co-gels increase the therapeutic potentials of MSCs on AKI. In vitro studies indicated that the co-gels enhanced the paracrine effects of MSCs, and significantly reduced the apoptosis of MSCs under oxidative environments...
October 13, 2017: Journal of Biomaterials Science. Polymer Edition
https://www.readbyqxmd.com/read/28967916/organoid-cystogenesis-reveals-a-critical-role-of-microenvironment-in-human-polycystic-kidney%C3%A2-disease
#20
Nelly M Cruz, Xuewen Song, Stefan M Czerniecki, Ramila E Gulieva, Angela J Churchill, Yong Kyun Kim, Kosuke Winston, Linh M Tran, Marco A Diaz, Hongxia Fu, Laura S Finn, York Pei, Jonathan Himmelfarb, Benjamin S Freedman
Polycystic kidney disease (PKD) is a life-threatening disorder, commonly caused by defects in polycystin-1 (PC1) or polycystin-2 (PC2), in which tubular epithelia form fluid-filled cysts. A major barrier to understanding PKD is the absence of human cellular models that accurately and efficiently recapitulate cystogenesis. Previously, we have generated a genetic model of PKD using human pluripotent stem cells and derived kidney organoids. Here we show that systematic substitution of physical components can dramatically increase or decrease cyst formation, unveiling a critical role for microenvironment in PKD...
October 2, 2017: Nature Materials
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