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Toxic Responses of the Kidney
Published in Stephen K. Hall, Joana Chakraborty, Randall J. Ruch, Chemical Exposure and Toxic Responses, 2020
The afferent arteriole delivers blood under high pressure to the glomerulus where selective filtration occurs. Hydrostatic pressure is the primary force responsible for the production of the glomerular filtrate. The filtration barrier consists of (1) the fenestrated endothelial cells lining the glomerular capillary, (2) epithelial podocyte foot processes, and (3) the intervening basement membrane derived from both the glomerular endothelium and supporting epithelial podocytic cells. Since this barrier is composed of cells with holes (fenestrated endothelium) or slits (podocyte foot processes), the selectivity of glomerular filtration is accomplished by the fused basement membranes. Ultrastructurally, the basement membrane has three components. The central layer is electrondense, contains fibers (type IV collagen), and is termed the lamina densa. The two outer most layers are more electron-lucent and are termed lamina rara interna, and externa. Materials which pass through the filter are limited to small molecular size and net molecular charge.
Kidney Structure and Physiology
Published in Joseph D. Bronzino, Donald R. Peterson, Biomedical Engineering Fundamentals, 2019
Joel M. Henderson and Mostafa Belghasem
FIGURE 2.3 (a) Photomicrograph of a human glomerulus from a section of formalin-xed, paran-embedded tissue. Many cross sections of glomerular capillaries (“capillary loops”) are evident (asterisks). e Bowman’s capsule (BC) surrounds the glomerular tu and denes the Bowman’s space between these two structures (BS). An arteriole (A) enters the vascular pole on the lower right. Periodic acid-Schi; bar = 50 μm. (b) Transmission electron micrograph (TEM) of a segment of a human glomerulus. e wall of a single capillary in cross section is demarcated by arrows from within the lumen. Note the cell body of a podocyte (P) protruding into the Bowman’s space (BS), red blood cell (R) within the lumen of a capillary, mesangium with a mesangial cell (M), and cell body of an endothelial cell (E) lining a capillary wall. Bar = 5 μm. (c) High magnication TEM of a section of a glomerular capillary wall. In this image, water and small solutes move across this ltration barrier from the capillary lumen at the bottom (L) to the Bowman’s space at the top (BS). FP, podocyte foot processes (seen in cross section); AB, actin bundle (seen in cross section); SD, ltration slit diaphragm; GBM, glomerular basement membrane; EC, endothelial cell; and F, endothelial cell fenestrae. Bar = 300 nm. (d) Scanning electron micrograph of the exterior of a glomerular capillary segment. e surface of the capillary is covered with interlocking podocyte foot processes (FP), which are branching o of major processes (MP). e major processes, in turn, arise from the podocyte cell body (P). Bar = 5 μm.
CRISPR-Based Genome Engineering in Human Stem Cells
Published in Deepak A. Lamba, Patient-Specific Stem Cells, 2017
Thelma Garcia, Deepak A. Lamba
A study compared various corrections methods to repair gene defect in Duchenne muscular dystrophy (Li et al., 2015b). Duchenne muscular dystrophy is a severe form of muscle degenerative disease caused by a mutation in the dystrophin gene. The authors tried three correction methods including exon skipping, frameshifting, and exon knockin and reported that exon knockin works best. The group further confirmed that following differentiation, the generated skeletal muscles expressed full-length version of dystrophin protein. A recent publication reported modeling a number of kidney defects in three-dimensional (3D) culture systems following CRISPR-mediated gene knockouts (Freedman et al., 2015). The group reported that the CRISPR–Cas9 knockout of podocalyxin gene in the iPSCs caused junctional organization defects in podocyte-like cells in the 3D kidney cultures, while knocking out of the polycystic kidney disease genes PKD1 or PKD2 induced cyst formation from kidney tubules in these cultures. A new report recently looked at repairing a mutation associated with deafness (Chen et al., 2016). They generated iPSCs from members of a Chinese family carrying MYO15A c.4642G>A and c.8374G>A mutations. These iPSC lines upon differentiation generated hair cells with abnormal morphology. The authors then corrected the mutations in the patient iPSC lines using CRISPR, which resulted in the restoration of hair cell morphology and function in differentiated hair cells.
Regulation of stem cell fate and function by using bioactive materials with nanoarchitectonics for regenerative medicine
Published in Science and Technology of Advanced Materials, 2022
Wei Hu, Jiaming Shi, Wenyan Lv, Xiaofang Jia, Katsuhiko Ariga
As shown in Figure 11, Homan et al. used 3D-printed millifluidic chips to house the developing kidney organoids embedded in engineered ECM [174]. Under high fluid flow, kidney organoids showed enhanced vascularization and increased mature perfusable lumens, podocyte and tubular compartment morphogenesis compared with that in static controls. Fluid flow inducing vascularization and morphological maturation of kidney organoids in vitro provides a new dimension for studies of kidney development, disease, and regeneration.