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https://www.readbyqxmd.com/read/29789935/potential-use-of-stem-cells-as-a-therapy-for-cystinosis
#1
REVIEW
Celine J Rocca, Stephanie Cherqui
Cystinosis is an autosomal recessive metabolic disease that belongs to the family of lysosomal storage disorders (LSDs). Initial symptoms of cystinosis correspond to the renal Fanconi syndrome. Patients then develop chronic kidney disease and multi-organ failure due to accumulation of cystine in all tissue compartments. LSDs are commonly characterized by a defective activity of lysosomal enzymes. Hematopoietic stem and progenitor cell (HSPC) transplantation is a treatment option for several LSDs based on the premise that their progeny will integrate in the affected tissues and secrete the functional enzyme, which will be recaptured by the surrounding deficient cells and restore physiological activity...
May 22, 2018: Pediatric Nephrology: Journal of the International Pediatric Nephrology Association
https://www.readbyqxmd.com/read/29779043/glis1-3-transcription-factors-critical-roles-in-the-regulation-of-multiple-physiological-processes-and-diseases
#2
REVIEW
Anton M Jetten
Krüppel-like zinc finger proteins form one of the largest families of transcription factors. They function as key regulators of embryonic development and a wide range of other physiological processes, and are implicated in a variety of pathologies. GLI-similar 1-3 (GLIS1-3) constitute a subfamily of Krüppel-like zinc finger proteins that act either as activators or repressors of gene transcription. GLIS3 plays a critical role in the regulation of multiple biological processes and is a key regulator of pancreatic β cell generation and maturation, insulin gene expression, thyroid hormone biosynthesis, spermatogenesis, and the maintenance of normal kidney functions...
May 19, 2018: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/29758394/impact-of-thrombotic-microangiopathy-on-renal-outcomes-and-survival-after-hematopoietic-stem-cell-transplantation
#3
Merve Postalcioglu, Haesook T Kim, Faruk Obut, Osman Arif Yilmam, Jiqiao Yang, Benjamin C Byun, Sophie Kupiec-Weglinski, Robert Soiffer, Jerome Ritz, Joseph H Antin, Edwin Alyea, John Koreth, Corey Cutler, Philippe Armand, Julie M Paik, David E Leaf, Vincent T Ho, Reza Abdi
Transplantation-associated thrombotic microangiopathy (TA-TMA) is a serious complication of hematopoietic stem cell transplantation (HSCT). We characterized the incidence, risk factors, and long-term outcomes associated with TA-TMA by performing a comprehensive review of all adult patients (n=1,990) undergoing allogeneic HSCT at the Dana Farber Cancer Institute/Brigham and Women's Hospital between 2005 and 2013. Using the City of Hope criteria, we identified 258 (13%) and 508 (26%) patients with "definite" and "probable" TMA, respectively...
May 11, 2018: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/29749549/enhanced-proliferation-and-differentiation-of-ho-1-gene-modified-bone-marrow-derived-mesenchymal-stem-cells-in-the-acute-injured-kidney
#4
Nanmei Liu, Huiling Wang, Guofeng Han, Jin Cheng, Weifeng Hu, Jinyuan Zhang
The aim of the present study was to investigate the effect of heme oxygenase-1 (HO-1) overexpression on the survival and differentiation ability of bone marrow‑derived mesenchymal stem cells (BMSCs) in the acute kidney injury (AKI) microenvironment. HO-1-BMSCs and enhanced green fluorescent protein (eGFP)-BMSCs were constructed. Rat ischemia/reperfusion (I/R)‑AKI-kidney homogenate supernatant was prep-ared to treat the BMSCs, eGFP-BMSCs and HO-1-BMSCs in vitro. In the AKI microenvironment, the HO-1-BMSCs exhibited a smaller proportion of cells at the G0/G1 phase, and a larger proportion of cells expressing proliferating cell nuclear antigen (PCNA) and cytokeratin 18 (CK18)...
May 11, 2018: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29743501/a-phase-i-clinical-trial-with-ex-vivo-expanded-recipient-regulatory-t-cells-in-living-donor-kidney-transplants
#5
James M Mathew, Jessica H-Voss, Ann LeFever, Iwona Konieczna, Cheryl Stratton, Jie He, Xuemei Huang, Lorenzo Gallon, Anton Skaro, Mohammed Javeed Ansari, Joseph R Leventhal
There is considerable interest in therapeutic transfer of regulatory T cells (Tregs) for controlling aberrant immune responses. Initial clinical trials have shown the safety of Tregs in hematopoietic stem cell transplant recipients and subjects with juvenile diabetes. Our hypothesis is that infusion(s) of Tregs may induce transplant tolerance thus avoiding long-term use of toxic immunosuppressive agents that cause increased morbidity/mortality. Towards testing our hypothesis, we conducted a phase I dose escalation safety trial infusing billions of ex vivo expanded recipient polyclonal Tregs into living donor kidney transplant recipients...
May 9, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29740333/flavonoids-in-kidney-health-and-disease
#6
REVIEW
Félix Vargas, Paola Romecín, Ana I García-Guillén, Rosemary Wangesteen, Pablo Vargas-Tendero, M Dolores Paredes, Noemí M Atucha, Joaquín García-Estañ
This review summarizes the latest advances in knowledge on the effects of flavonoids on renal function in health and disease. Flavonoids have antihypertensive, antidiabetic, and antiinflammatory effects, among other therapeutic activities. Many of them also exert renoprotective actions that may be of interest in diseases such as glomerulonephritis, diabetic nephropathy, and chemically-induced kidney insufficiency. They affect several renal factors that promote diuresis and natriuresis, which may contribute to their well-known antihypertensive effect...
2018: Frontiers in Physiology
https://www.readbyqxmd.com/read/29737200/human-peripheral-blood-mononuclear-cells-incubated-in-vasculogenic-conditioning-medium-dramatically-improve-ischemia-reperfusion-acute-kidney-injury-in-mice
#7
Takayasu Ohtake, Shuzo Kobayashi, Shimon Slavin, Yasuhiro Mochida, Kunihiro Ishioka, Hidekazu Moriya, Sumi Hidaka, Ryo Matsuura, Maki Sumida, Daisuke Katagiri, Eisei Noiri, Kayoko Okada, Hiroshi Mizuno, Rica Tanaka
Acute kidney injury (AKI) is a major clinical problem that still has no established treatment. We investigated the efficacy of cultured human peripheral blood mononuclear cells (PBMNCs) for AKI. Ischemia/reperfusion injury (IRI) was used to induce AKI in male nonobese diabetic (NOD/severe combined immunodeficiency) mice aged 7 to 8 wk. PBMNCs were isolated from healthy volunteers and were subjected to quality and quantity controlled (QQc) culture for 7 d in medium containing stem cell factor, thrombopoietin, Flt-3 ligand, vascular endothelial growth factor, and interleukin 6...
January 1, 2018: Cell Transplantation
https://www.readbyqxmd.com/read/29733407/bone-inflammation-and-the-bone-marrow-niche-in-chronic-kidney-disease-what-do-we-know
#8
Sandro Mazzaferro, Giuseppe Cianciolo, Antonio De Pascalis, Chiara Guglielmo, Pablo A Urena Torres, Jordi Bover, Lida Tartaglione, Marzia Pasquali, Gaetano La Manna
Recent improvements in our understanding of physiology have altered the way in which bone is perceived: no longer is it considered as simply the repository of divalent ions, but rather as a sophisticated endocrine organ with potential extraskeletal effects. Indeed, a number of pathologic conditions involving bone in different ways can now be reconsidered from a bone-centred perspective. For example, in metabolic bone diseases like osteoporosis (OP) and renal osteodystrophy (ROD), the association with a worse cardiovascular outcome can be tentatively explained by the possible derangements of three recently discovered bone hormones (osteocalcin, fibroblast growth factor 23 and sclerostin) and a bone-specific enzyme (alkaline phosphatase)...
May 4, 2018: Nephrology, Dialysis, Transplantation
https://www.readbyqxmd.com/read/29724174/eculizumab-as-salvage-therapy-for-recurrent-monoclonal-gammopathy-induced-c3-glomerulopathy-in-a-kidney-allograft
#9
Philipp Moog, Philipp J Jost, Maike Büttner-Herold
BACKGROUND: Monoclonal gammopathy causes several kinds of renal pathology. A rare and special form is monoclonal gammopathy-induced C3 glomerulopathy (MG-C3G). Like idiopathic C3G, MG-C3G frequently leads to end-stage renal disease. MG-C3G frequently recurs after renal transplantation, leading to graft failure in most of the patients. While there is some evidence for successful treatment of recurrent idiopathic C3 glomerulopathy with eculizumab after renal transplantation, nothing is known about its efficacy in the setting of recurrent MG-C3G...
May 3, 2018: BMC Nephrology
https://www.readbyqxmd.com/read/29720573/parabiosis-and-single-cell-rna-sequencing-reveal-a-limited-contribution-of-monocytes-to-myofibroblasts-in-kidney-fibrosis
#10
Rafael Kramann, Flavia Machado, Haojia Wu, Tetsuro Kusaba, Konrad Hoeft, Rebekka K Schneider, Benjamin D Humphreys
Fibrosis is the common final pathway of virtually all chronic injury to the kidney. While it is well accepted that myofibroblasts are the scar-producing cells in the kidney, their cellular origin is still hotly debated. The relative contribution of proximal tubular epithelium and circulating cells, including mesenchymal stem cells, macrophages, and fibrocytes, to the myofibroblast pool remains highly controversial. Using inducible genetic fate tracing of proximal tubular epithelium, we confirm that the proximal tubule does not contribute to the myofibroblast pool...
May 3, 2018: JCI Insight
https://www.readbyqxmd.com/read/29706353/patient-ipsc-derived-kidney-organoids-show-functional-validation-of-a-ciliopathic-renal-phenotype-and-reveal-underlying-pathogenetic-mechanisms
#11
Thomas A Forbes, Sara E Howden, Kynan Lawlor, Belinda Phipson, Jovana Maksimovic, Lorna Hale, Sean Wilson, Catherine Quinlan, Gladys Ho, Katherine Holman, Bruce Bennetts, Joanna Crawford, Peter Trnka, Alicia Oshlack, Chirag Patel, Andrew Mallett, Cas Simons, Melissa H Little
Despite the increasing diagnostic rate of genomic sequencing, the genetic basis of more than 50% of heritable kidney disease remains unresolved. Kidney organoids differentiated from induced pluripotent stem cells (iPSCs) of individuals affected by inherited renal disease represent a potential, but unvalidated, platform for the functional validation of novel gene variants and investigation of underlying pathogenetic mechanisms. In this study, trio whole-exome sequencing of a prospectively identified nephronophthisis (NPHP) proband and her parents identified compound-heterozygous variants in IFT140, a gene previously associated with NPHP-related ciliopathies...
April 21, 2018: American Journal of Human Genetics
https://www.readbyqxmd.com/read/29703972/critically-ill-allogenic-hsct-patients-in-the-intensive-care-unit-a-systematic-review-and-meta-analysis-of-prognostic-factors-of-mortality
#12
Colombe Saillard, Michael Darmon, Magali Bisbal, Antoine Sannini, Laurent Chow-Chine, Marion Faucher, Etienne Lengline, Norbert Vey, Didier Blaise, Elie Azoulay, Djamel Mokart
Outcome of patients undergoing allogenic hematopoietic stem cell transplantation (allo-HSCT) has improved. To investigate if this improvement can be transposed to the ICU setting, we conducted a systematic review and meta-analysis to assess short-term mortality of critically ill allo-HSCT patients admitted to the ICU and to identify prognostic factors of mortality. Public-domain electronic databases, including Medline via PubMed and the Cochrane Library were searched. All full-text articles written-English studies published from 2006 to 2016, including allo-HSCT adults transferred to the ICU were included...
April 27, 2018: Bone Marrow Transplantation
https://www.readbyqxmd.com/read/29701108/acute-kidney-injury-as-a-condition-of-renal-senescence
#13
Lucia Andrade, Camila E Rodrigues, Samirah A Gomes, Irene L Noronha
Acute kidney injury (AKI), characterized by a sharp drop in glomerular filtration, continues to be a significant health burden because it is associated with high initial mortality, morbidity, and substantial health-care costs. There is a strong connection between AKI and mechanisms of senescence activation. After ischemic or nephrotoxic insults, a wide range of pathophysiological events occur. Renal tubular cell injury is characterized by cell membrane damage, cytoskeleton disruption, and DNA degradation, leading to tubular cell death by necrosis and apoptosis...
January 1, 2018: Cell Transplantation
https://www.readbyqxmd.com/read/29695308/the-presence-of-human-mesenchymal-stem-cells-of-renal-origin-in-amniotic-fluid-increases-with-gestational-time
#14
Md Shaifur Rahman, Lucas-Sebastian Spitzhorn, Wasco Wruck, Carsten Hagenbeck, Percy Balan, Nina Graffmann, Martina Bohndorf, Audrey Ncube, Pascale V Guillot, Tanja Fehm, James Adjaye
BACKGROUND: Established therapies for managing kidney dysfunction such as kidney dialysis and transplantation are limited due to the shortage of compatible donated organs and high costs. Stem cell-based therapies are currently under investigation as an alternative treatment option. As amniotic fluid is composed of fetal urine harboring mesenchymal stem cells (AF-MSCs), we hypothesized that third-trimester amniotic fluid could be a novel source of renal progenitor and differentiated cells...
April 25, 2018: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/29689547/sirt3-facilitates-amniotic-fluid-stem-cells-to-repair-diabetic-nephropathy-through-protecting-mitochondrial-homeostasis-by-modulation-of-mitophagy
#15
Jianxun Feng, Chang Lu, Qin Dai, Junqin Sheng, Min Xu
BACKGROUND/AIMS: Amniotic fluid stem cells (AFSCs) transplantation is a promising therapeutic strategy for diabetic nephropathy. Sirtuin3 (SIRT3) is a novel mitochondrial protective factor. In the present study, we aimed to investigate whether SIRT3 protects against hyperglycemia-induced AFSCs damage and enhances the therapeutic efficiency of AFSCs in diabetic nephropathy. METHODS: To establish the diabetic nephropathy model, db/ db mice were used. AFSCs were obtained and transplanted into the kidney tissue of db/ db mice...
April 19, 2018: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29686294/development-of-new-method-to-enrich-human-ipsc-derived-renal-progenitors-using-cell-surface-markers
#16
Azusa Hoshina, Tatsuya Kawamoto, Shin-Ichi Sueta, Shin-Ichi Mae, Toshikazu Araoka, Hiromi Tanaka, Yasunori Sato, Yukiko Yamagishi, Kenji Osafune
Cell therapy using renal progenitors differentiated from human embryonic stem cells (hESCs) or induced pluripotent stem cells (hiPSCs) has the potential to significantly reduce the number of patients receiving dialysis therapy. However, the differentiation cultures may contain undifferentiated or undesired cell types that cause unwanted side effects, such as neoplastic formation, when transplanted into a body. Moreover, the hESCs/iPSCs are often genetically modified in order to isolate the derived renal progenitors, hampering clinical applications...
April 23, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29679772/efficacy-of-cidofovir-in-treatment-of-bk-virus-induced-hemorrhagic-cystitis-in-post-allogeneic-hematopoietic-cell-transplant-recipients
#17
Eric A Coomes, Amanda Jacques Wolfe, Fotios V Michelis, Dennis Dong-Hwong Kim, Santhosh Thyagu, Auro Viswabandya, Jeffrey H Lipton, Hans A Messner, Uday Deotare
BACKGROUND: BK virus associated hemorrhagic cystitis (BK-HC) is a common complication after allogeneic hematopoietic stem cell transplantation (allo-HCT), with incidence up to 70%. Cidofovir is an antiviral agent with growing evidence as a therapeutic intervention. OBJECTIVE: To assess the safety profile and efficacy of intravenous and intravesical cidofovir in allo-HCT patients with BK-HC. METHODS: Retrospective study of the allo-HCT cohort who received cidofovir for symptomatic BK-HC (hematuria with BK viruria or viremia) from January 2010 until March 2017 in a single transplant center in Ontario, Canada...
April 18, 2018: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/29668344/phenotypic-plasticity-of-mesenchymal-stem-cells-is-crucial-for-mesangial-repair-in-a-model-of-immunoglobulin-light-chain-associated-mesangial-damage
#18
Guillermo A Herrera, Jiamin Teng, Chun Zeng, Hongzhi Xu, Man Liang, J Steven Alexander, Bing Liu, Chris Boyer, Elba A Turbat-Herrera
Mesangiopathies produced by glomerulopathic monoclonal immunoglobulin light chains (GLCs) acting on the glomerular mesangium produce two characteristic lesions: AL-amyloidosis (AL-Am) and light chain deposition disease (LCDD). In both cases, the pathology is centered in the mesangium, where initial and progressive damage occurs. In AL-Am the mesangial matrix is destroyed and replaced by amyloid fibrils and in LCDD, the mesangial matrix is increased and remodeled. The collagen IV rich matrix is replaced by tenascin...
April 18, 2018: Ultrastructural Pathology
https://www.readbyqxmd.com/read/29666052/functional-comparison-of-distinct-brachyury-states-in-a-renal-differentiation-assay
#19
Jing Zhou, Antonius Plagge, Patricia Murray
Mesodermal populations can be generated in vitro from mouse embryonic stem cells (mESCs) using three-dimensional (3-D) aggregates called embryoid bodies or two-dimensional (2-D) monolayer culture systems. Here, we investigated whether Brachyury -expressing mesodermal cells generated using 3-D or 2-D culture systems are equivalent, or instead, have different properties. Using a Brachyury -GFP/E2-Crimson reporter mESC line, we isolated Brachyury- GFP+ mesoderm cells using flow-activated cell sorting and compared their gene expression profiles and ex vivo differentiation patterns...
April 17, 2018: Biology Open
https://www.readbyqxmd.com/read/29651604/patterns-and-frequency-of-renal-abnormalities-in-fanconi-anaemia-implications-for-long-term-management
#20
Vijaya Sathyanarayana, Beth Lee, Neville B Wright, Rui Santos, Denise Bonney, Robert Wynn, Leena Patel, Kate Chandler, Ed Cheesman, Detlev Schindler, Nicholas J A Webb, Stefan Meyer
BACKGROUND: Fanconi anaemia (FA) is an inherited disease with bone marrow failure, variable congenital and developmental abnormalities, and cancer predisposition. With improved survival, non-haematological manifestations of FA become increasingly important for long-term management. While renal abnormalities are recognized, detailed data on patterns and frequency and implications for long-term management are sparse. METHODS: We reviewed clinical course and imaging findings of FA patients with respect to renal complications in our centre over a 25-year period to formulate some practical suggestions for guidelines for management of renal problems associated with FA...
April 12, 2018: Pediatric Nephrology: Journal of the International Pediatric Nephrology Association
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