Abstract:
:Development of physiologically relevant cellular models with strong translatability to human pathophysiology is critical for identification and validation of novel therapeutic targets. Herein we describe a detailed protocol for generation of an advanced 3-dimensional kidney cellular model using induced pluripotent stem cells, where differentiation and maturation of kidney progenitors and podocytes can be monitored in live cells due to CRISPR/Cas9-mediated fluorescent tagging of kidney lineage markers (SIX2 and NPHS1). Utilizing these cell lines, we have refined the previously published procedures to generate a new, higher throughput protocol suitable for drug discovery. Using paraffin-embedded sectioning and whole-mount immunostaining, we demonstrated that organoids grown in suspension culture express key markers of kidney biology (WT1, ECAD, LTL, nephrin) and vasculature (CD31) within renal cortical structures with microvilli, tight junctions and podocyte foot processes visualized by electron microscopy. Additionally, the organoids resemble the adult kidney transcriptomics profile, thereby strengthening the translatability of our in vitro model. Thus, development of human nephron-like structures in vitro fills a major gap in our ability to assess the effect of potential treatment on key kidney structures, opening up a wide range of possibilities to improve clinical translation.
journal_name
Kidney Intjournal_title
Kidney internationalauthors
Boreström C,Jonebring A,Guo J,Palmgren H,Cederblad L,Forslöw A,Svensson A,Söderberg M,Reznichenko A,Nyström J,Patrakka J,Hicks R,Maresca M,Valastro B,Collén Adoi
10.1016/j.kint.2018.05.003subject
Has Abstractpub_date
2018-12-01 00:00:00pages
1099-1110issue
6eissn
0085-2538issn
1523-1755pii
S0085-2538(18)30356-9journal_volume
94pub_type
杂志文章abstract::Direct-acting antivirals have revolutionized the treatment of hepatitis C virus (HCV) infection in patients with chronic kidney disease, with implications for the timing of antiviral treatment among kidney transplant candidates and for the use of HCV viremic donors. A recent consensus conference reviewed the available...
journal_title:Kidney international
pub_type: 评论,杂志文章
doi:10.1016/j.kint.2017.09.002
更新日期:2017-11-01 00:00:00
abstract:BACKGROUND:Hypercholesterolemia may affect both endothelial function and arterial distensibility (DC). Renal transplant recipients (NTX) exhibit advanced structural and functional alterations of arterial vessel walls. The aim of this double-blind, randomized trial was to evaluate the effects of fluvastatin (FLU) on bra...
journal_title:Kidney international
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1046/j.1523-1755.2001.0590041473.x
更新日期:2001-04-01 00:00:00
abstract::Transplanted organs express allogeneic epitopes against which a recipient's immune system mounts a destructive response. In the absence of a reliable strategy for induction of donor-specific tolerance, therapeutic immunosuppression remains the best prospect to prevent rejection, but exposes recipients to increased ris...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2015.268
更新日期:2015-12-01 00:00:00
abstract::The kidney is a likely source for some urinary epinephrine (E) since adrenalectomized animals and humans continue to excrete urinary E and the human kidney contains E synthesizing enzymes. We studied subjects during an intravenous infusion of 3H-E to determine the fraction of urinary E derived from the kidney. Eight n...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1997.40
更新日期:1997-01-01 00:00:00
abstract::Severe segmental glomerulonephritis (Seg GN) (greater than or equal to 50% involvement) in systemic lupus erythematosus (SLE) is classified as diffuse GN (DPGN) in the WHO classification. We tested the validity of the assumption that severe Seg GN and DPGN have the same prognosis by determining the proportion of glome...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1987.203
更新日期:1987-08-01 00:00:00
abstract::Endostatin (EST), an antiangiogenic factor, is enriched in aging kidneys. EST is also an interactive partner of transglutaminase 2 (TG2), an enzyme that cross-links extracellular matrix proteins. Here we tested whether EST and TG2 play a role in the fibrosis of aging. In wild-type mice, aging kidneys exhibited a 2- to...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1016/j.kint.2016.01.030
更新日期:2016-06-01 00:00:00
abstract:BACKGROUND:Our purpose was to compare the function and complications of two high-flow polyurethane hemodialysis catheters. METHODS:This prospective, randomized trial compared the Ash-Split (MedComp) and Opti-Flow (Bard Access Systems) catheters. All patients referred for tunneled hemodialysis catheter placement were o...
journal_title:Kidney international
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1046/j.1523-1755.2002.00416.x
更新日期:2002-07-01 00:00:00
abstract:BACKGROUND:The next phase of the molecular revolution will bring functional genomics down to the level of individual cells in a tissue. Laser capture microdissection (LCM) coupled with reverse transcription-polymerase chain reaction (RT-PCR) can measure gene expression in normal, cancerous, injured, or fibrotic tissue....
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.2000.00295.x
更新日期:2000-09-01 00:00:00
abstract::Intercellular adhesion molecule-1 (ICAM-1) and MHC class II (Ia) antigens are increased on proximal tubular epithelial cells (TEC) in autoimmune nephritis and transplant rejection. ICAM-1 is a member of the immunoglobulin gene superfamily that increases the avidity of T cell interactions with antigen-presenting cells ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1990.221
更新日期:1990-09-01 00:00:00
abstract:BACKGROUND:The mechanisms of cyclosporine (CsA)-induced nephrotoxicity are not fully understood. While hemodynamic changes may be involved in vivo, there is also some evidence for tubular involvement. We previously showed direct toxicity of CsA in the LLC-PK1 renal tubular cell line. In the current study we examined me...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.1998.00202.x
更新日期:1998-12-01 00:00:00
abstract::Angiotensin II plays an important role in the regulation of blood pressure, body salt and fluid balance, and urine concentration. Mice with deletion of the AT(1a) receptor develop polyuria and urine concentration defects. We studied the mechanisms of these urine concentration defects by treating wild-type and AT(1a)-k...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2009.134
更新日期:2009-07-01 00:00:00
abstract::The recent identification of RPGRIP1L as a Joubert syndrome gene brings the total of known genes to five. Three of these are also associated with the lethal Meckel syndrome, and two with Senior-Løken syndrome; both of these disorders share Joubert syndrome phenotypes, illustrating the genetic complexity of this. ...
journal_title:Kidney international
pub_type: 杂志文章,评审
doi:10.1038/sj.ki.5002577
更新日期:2007-12-01 00:00:00
abstract::The relationship between commonly occurring genetic variants (G1 and G2) in the APOL1 gene in African Americans and different disease traits, such as kidney disease, cardiovascular disease, and pre-eclampsia, remains the subject of controversy. Here we took a genotype-first approach, a phenome-wide association study, ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1016/j.kint.2020.01.027
更新日期:2020-05-01 00:00:00
abstract::Renal ischemia-reperfusion injury is a leading cause of acute kidney injury; the pathogenesis of which remains poorly understood and effective therapies are still lacking. Here we tested whether microRNAs, identified as critical regulators of cell health and disease, are involved in this process. We found that miR-17-...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1016/j.kint.2016.07.017
更新日期:2017-01-01 00:00:00
abstract::Recent insights have defined the central role of podocytes both in rare genetic diseases and as a general determinant of the progression of human glomerular diseases. In a recent issue of Nature, Weavers et al. described a podocyte-like cell type in Drosophila, the nephrocyte, that closely resembles mammalian podocyte...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2008.653
更新日期:2009-03-01 00:00:00
abstract::Acute kidney injury (AKI) following cardiac surgery is closely interrelated with hemodynamic instability and sympathetic activity, and adversely influences prognosis. Here, we investigated in a randomized placebo-controlled trial whether dexmedetomidine, an α2 adrenoreceptor agonist, could prevent AKI after valvular h...
journal_title:Kidney international
pub_type: 杂志文章,随机对照试验
doi:10.1038/ki.2015.306
更新日期:2016-03-01 00:00:00
abstract::A morphometric technique is used to estimate the absolute and relative surface areas of the brush border microvilli and cell walls bordering lateral intercellular spaces. In isolated, perfused proximal tubule from rabbit, the luminal and lateral surfaces are equal in area. For proximal convoluted tubules (PCT) each su...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1975.125
更新日期:1975-12-01 00:00:00
abstract::Long-term (5 years) treatment of 20 growth-retarded pre-pubertal children with chronic renal insufficiency (CRI) led to a significant (P < 0.00005) improvement in standardized height from -2.6 at baseline to -0.7 at five years. Eight patients were paused after reaching target height (50th centile midparental height) a...
journal_title:Kidney international
pub_type: 临床试验,杂志文章,多中心研究,随机对照试验
doi:10.1038/ki.1996.108
更新日期:1996-03-01 00:00:00
abstract::The cannabinoid receptor type 2 (CB2) is a G protein-coupled seven transmembrane receptor that transmits endogenous cannabinoid signaling. The role of CB2 in the pathogenesis of kidney injury and fibrosis remains poorly understood. Here we demonstrate that CB2 was induced, predominantly in kidney tubular epithelium, i...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1016/j.kint.2018.05.023
更新日期:2018-10-01 00:00:00
abstract::The enzyme 11 beta-hydroxysteroid dehydrogenase (11 beta-OHSD) is thought to be a protective enzyme of the mineralocorticoid receptor (MR). We have previously demonstrated (Bonvalet et al, J Clin Invest 86:832-837, 1990) that 11 beta-OHSD is colocalized with MR along the rabbit nephron. In the present study, we examin...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1992.260
更新日期:1992-07-01 00:00:00
abstract::Although the pathogenesis of steroid-sensitive nephrotic syndrome (SSNS) remains elusive, multiple epidemiologic, clinical, and experimental studies converge on the common theme of immune dysregulation. Initially, T-cell adaptive immunity was solely emphasized; however, the role of humoral immunity in nephrotic syndro...
journal_title:Kidney international
pub_type: 评论,杂志文章
doi:10.1016/j.kint.2019.05.031
更新日期:2019-10-01 00:00:00
abstract:BACKGROUND:Edaravone (3-methyl-1-phenyl-2-pyrazolin-5-one) is a potent scavenger of free radicals and has the antioxidant ability to inhibit lipid peroxidation. Its protective effect on brain ischemia has been shown. This study aimed to elucidate its possible therapeutic effects on renal oxidative stress in a rat ische...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1111/j.1523-1755.2004.00567.x
更新日期:2004-05-01 00:00:00
abstract:BACKGROUND:Recently, we observed that the severity of glomerulonephritis in an experimental model of immunoglobulin A nephropathy (IgAN) induced by Sendai virus differs between C57BL/6 and BALB/c mouse strains. The determinants of differing renal insufficiency are not understood. In the present study, we examine the ca...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.2003.00258.x
更新日期:2003-11-01 00:00:00
abstract::Cell surface aminopeptidases N (APN) and A (APA) have been characterized on cultured human glomerular epithelial cells and a SV40-transformed cell line derived from them. APN had a wide substrate specificity whereas APA only attacked peptides with an acidic N terminal amino acid. Both enzymes also differed by their se...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1992.227
更新日期:1992-06-01 00:00:00
abstract:BACKGROUND:Tacrolimus has a narrow therapeutic window, and bioavailability is known to vary considerably between renal transplant recipients. Most centers still rely on measurement of trough levels, but there are conflicting reports on the correlation between tacrolimus trough levels and systemic exposure, as measured ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1111/j.1523-1755.2005.00352.x
更新日期:2005-06-01 00:00:00
abstract:BACKGROUND:A family history increases the risk of kidney stone passage independent of dietary risk factors. However, the metabolic basis for familial aggregation of urolithiasis is unknown. METHODS:We evaluated metabolic risk factors in families with at least two sibs with a history of calcium stones. Sibs underwent o...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.2001.0600031141.x
更新日期:2001-09-01 00:00:00
abstract::Hyperinsulinemia can contribute to hypertension through effects on sodium transport. To test whether the stimulatory effect of insulin on renal proximal tubule sodium transport is preserved in insulin resistance, we compared the effects of insulin on abdominal adipocytes and proximal tubules in rats and humans. Insuli...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2014.351
更新日期:2015-03-01 00:00:00
abstract::The adjuvanted hepatitis B vaccine, HB-AS04, elicits more rapid and persistent protective antibody concentrations than double doses of conventional recombinant vaccines in patients with renal insufficiency. We compared the immunogenicity, reactogenicity, and safety of the AS02(V)-adjuvanted hepatitis B vaccine HB-AS02...
journal_title:Kidney international
pub_type: 杂志文章,随机对照试验
doi:10.1038/ki.2009.454
更新日期:2010-02-01 00:00:00
abstract:BACKGROUND:Low birth weight is an important risk factor for hypertension and unfavorable prognoses of a number of renal diseases. It is also associated with reduced kidney size and nephron number. A differentiation between the effects of low birth weight versus being born premature or small for gestational age has, how...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1111/j.1523-1755.2005.00451.x
更新日期:2005-08-01 00:00:00
abstract::In adults on chronic hemodialysis, achieving a hemoglobin concentration of 12g/dl and above with erythropoiesis stimulating agents leads to increased cardiovascular events and mortality, but this may not be true in children. Therefore, we conducted a retrospective cohort study of pediatric patients (under 18) from the...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1016/j.kint.2016.09.013
更新日期:2017-01-01 00:00:00