Characterization of Growth, Glomerular Number, and Tubular Proteins in the Developing Rhesus Monkey Kidney

Batchelder, Cynthia A.; Keyser, Jennifer L.; Lee, C. Chang I.; Tarantal, Alice F.

doi:10.1002/ar.22756

Cited by 13 publications

(19 citation statements)

References 56 publications

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“…Cells lining the lumen of larger tubules typically displayed an epithelial morphology and expressed cytokeratin, but not vimentin ( Fig 5E–5H ). Early renal lineage markers WT1 and PAX2 were expressed in distinct regions under Protocol A on both types of scaffold materials ( Fig 5I and 5J ) in a pattern similar to mid- to late-first trimester kidney development where the PAX2-positive ureteric bud is surrounded by WT1-positive metanephric mesenchyme [ 28 ]. Under Protocol B, PAX2-positive cells surrounded WT1-positive tubules for cultures on renal ECM with a more diffuse staining pattern observed in PSS ( Fig 5K and 5L ).…”

Section: Resultsmentioning

confidence: 99%

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Natural Scaffolds for Renal Differentiation of Human Embryonic Stem Cells for Kidney Tissue Engineering

2015

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Despite the enthusiasm for bioengineering of functional renal tissues for transplantation, many obstacles remain before the potential of this technology can be realized in a clinical setting. Viable tissue engineering strategies for the kidney require identification of the necessary cell populations, efficient scaffolds, and the 3D culture conditions to develop and support the unique architecture and physiological function of this vital organ. Our studies have previously demonstrated that decellularized sections of rhesus monkey kidneys of all age groups provide a natural extracellular matrix (ECM) with sufficient structural properties with spatial and organizational influences on human embryonic stem cell (hESC) migration and differentiation. To further explore the use of decellularized natural kidney scaffolds for renal tissue engineering, pluripotent hESC were seeded in whole- or on sections of kidney ECM and cell migration and phenotype compared with the established differentiation assays for hESC. Results of qPCR and immunohistochemical analyses demonstrated upregulation of renal lineage markers when hESC were cultured in decellularized scaffolds without cytokine or growth factor stimulation, suggesting a role for the ECM in directing renal lineage differentiation. hESC were also differentiated with growth factors and compared when seeded on renal ECM or a new biologically inert polysaccharide scaffold for further maturation. Renal lineage markers were progressively upregulated over time on both scaffolds and hESC were shown to express signature genes of renal progenitor, proximal tubule, endothelial, and collecting duct populations. These findings suggest that natural scaffolds enhance expression of renal lineage markers particularly when compared to embryoid body culture. The results of these studies show the capabilities of a novel polysaccharide scaffold to aid in defining a protocol for renal progenitor differentiation from hESC, and advance the promise of tissue engineering as a source of functional kidney tissue.

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Section: Resultsmentioning

confidence: 99%

“…Analysis of immunohistochemical markers was carried out according to established protocols for glomerular, tubular, and renal developmental markers [ 27 , 28 ]. The primary antibodies utilized in the study are shown in Table 1 .…”

Section: Methodsmentioning

confidence: 99%

Natural Scaffolds for Renal Differentiation of Human Embryonic Stem Cells for Kidney Tissue Engineering

2015

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“…In the present study, stereological techniques were used for the quantification of volume, volume fraction, glomerular number, and PCT and DCT length of the cat kidney. Stereological methods are known as reliable, precise, and efficient methods for quantifying kidney structures, which contain important information about the renal function and organization (Nyengaard, ; Batchelder et al, ).…”

Section: Discussionmentioning

confidence: 99%

“…Most stereological investigations on the kidney have been carried out on laboratory animals such as mouse (Arsenault et al, ; Walton et al, ; Nuñez et al, ) and rat (Şimşek et al, ; Khoshvakhti et al, ; Melchioretto et al, ; Seravalli et al, ), and also on other mammals such as nonhuman primates (Gubhaju and Black, ; Batchelder et al, ). However, apart from investigations on the kidney in pig (Cibulskyte et al, ; Karstoft et al, ; Lødrup et al, ,b), sheep (Bains et al, ; Wintour et al, ) and horse (Bolat et al, ), the morphometric features of kidney of other domestic animals have not been thoroughly investigated using stereology.…”

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confidence: 99%

Cat Kidney Glomeruli and Tubules Evaluated by Design‐Based Stereology

Sadeghinezhad

Nyengaard

2019

The Anatomical Record

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Renal function is related to its structure and three‐dimensional structural parameters correlate better with the kidney function than two‐dimensional structural parameters. Stereology is the current gold‐standard technique for the morphometrical evaluation of kidney structures. This study describes morphometric features of the kidney of the cat using design‐based stereological techniques aimed to introduce the cat as a translational model in nephrology and provide basic findings for diagnosis and treatment of kidney diseases in this species. Left kidneys of four cats were included in the present study. The kidney volume, volume fraction of cortex and medulla, glomerular volume, glomerular mean volume, glomerular number, and proximal convoluted tubule (PCT) and distal convoluted tubule (DCT) length were estimated. The kidney volume was estimated to 11.4 ± 1.3 cm3. The volume fraction of cortex and medulla was 65.6 ± 2% and 34.2 ± 2%, respectively. The total number of glomeruli was estimated to be 186 ± 11 × 103 using the physical disector/fractionator method. The mean glomerular volume was estimated to be 1.54 ± 0.06 × 106 μm3 and the glomerular volume was covering 2.13 ± 0.34% of the whole kidney. The total length of PCT and DCT was estimated to be 2.26 ± 0.48 km and 505 ± 43 m, respectively. Our data might contribute to the knowledge of kidneys in mammals and provide a comparison with available data on human and other mammals. Anat Rec, 302:1846–1854, 2019. © 2019 American Association for Anatomy

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“…In the normal kidney, proximal tubules, rare Bowman's capsule epithelium, descending thin limbs of long looped nephrons, descending vasa recta, glomerular and vascular endothelium, and red blood cells had AQP1þ cytoplasmic and membrane immunostaining. [54][55][56] In the affected kidney, there were only a few small poorly differentiated cortical tubules that stained AQP1þ, although nests of morphologically mature proximal tubules stained positive. Also, occasional Bowman's capsule epithelium had increased AQP1þ immunostaining (not shown).…”

Section: Aquaporinmentioning

confidence: 99%

Congenital Unilateral Renal Aplasia in a Cynomolgus Monkey (Macaca fascicularis) With Investigation Into Potential Pathogenesis

et al. 2020

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We describe and characterize unilateral renal aplasia in a cynomolgus monkey ( Macaca fascicularis) from a chronic toxicology study adding to the limited histopathology reports of congenital renal anomalies in macaques. In the current case, the affected kidney was macroscopically small and characterized microscopically by a thin cortex with an underdeveloped medulla and an absent papilla. The remnant medulla lacked a corticomedullary junction and contained only a few irregular collecting duct-like structures. The cortex had extensive interstitial mature collagen deposition with fibromuscular collar formation around Bowman’s capsules. Due to parenchymal collapse, mature glomeruli were condensed together with occasional atrophic and sclerotic glomeruli. The majority of the cortical tubules were poorly differentiated with only small islands of fully developed cortical tubules present. Histochemical and immunohistochemical stains were utilized to demonstrate key diagnostic features of this congenital defect, to assist with differentiating it from renal dysplasia, and to provide potential mechanistic pathways. Immunostaining (S100, paired box gene 2 [PAX2], aquaporins) of the medulla was compatible with incomplete maturation associated with aplasia, while the immunostaining profile for the cortex (vimentin, calbindin, PAX2-positive cortical tubules, and smooth muscle actin–positive fibromuscular collars) was most compatible with dedifferentiation secondary to degenerative changes.

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Characterization of Growth, Glomerular Number, and Tubular Proteins in the Developing Rhesus Monkey Kidney

Cited by 13 publications

References 56 publications

Natural Scaffolds for Renal Differentiation of Human Embryonic Stem Cells for Kidney Tissue Engineering

Natural Scaffolds for Renal Differentiation of Human Embryonic Stem Cells for Kidney Tissue Engineering

Cat Kidney Glomeruli and Tubules Evaluated by Design‐Based Stereology

Congenital Unilateral Renal Aplasia in a Cynomolgus Monkey (Macaca fascicularis) With Investigation Into Potential Pathogenesis

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