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  • organs
  • BOSTON) - Toward the ultimate goal of engineering human tissues and organs that can mimic native function for use in drug screening, disease modeling, and regenerative medicine, a Wyss Institute team led by Core Faculty member Jennifer Lewis, Sc.D., has made another foundational advance using three-dimensional (3D) bioprinting. (harvard.edu)
  • As a fabrication platform, the approach is flexible, scalable, and adaptable, meaning that in addition to working towards larger, scaled-up kidney constructs, the team also plans to explore development of other types of complex functional human tissues and organs. (harvard.edu)
  • The kidneys are complex and critical organs. (biomedcentral.com)
  • How do animal cells assemble into tissues and organs? (pubmedcentralcanada.ca)
  • The defining feature of metazoa is that their cells are organized into multicellular tissues and organs. (pubmedcentralcanada.ca)
  • Many epithelial organs make use of interconnected tubular networks, although the basic design principles (as defined by Rafelski and Marshall 8 ) are the same: a series of tubes terminates in a spherical ending or cap, which is referred to as an acinus, end bud, alveolus or cyst in different tissues. (pubmedcentralcanada.ca)
  • this involves excretion (getting rid of metabolic nitrogen wastes and other substances such as hormones that would be toxic if allowed to accumulate in the blood) through organs such as the skin and the kidneys. (wikipedia.org)
  • epithelial cells
  • Now, in close collaboration with Roche scientist Annie Moisan, they have leveraged their bioprinting and materials expertise to construct a functional 3D renal architecture containing living human epithelial cells, which line the surface of tubules in the kidney. (harvard.edu)
  • Cuboidal epithelial cells lining the proximal tubule have extensive lateral interdigitations between neighboring cells, which lend an appearance of having no discrete cell margins when viewed with a light microscope. (wikipedia.org)
  • regulates
  • Parathyroid hormone regulates serum calcium through its effects on bone, kidney, and the intestine: In bone, PTH enhances the release of calcium from the large reservoir contained in the bones. (wikipedia.org)
  • PTH up-regulates 25-hydroxyvitamin D3 1-alpha-hydroxylase, the enzyme responsible for 1-alpha hydroxylation of 25-hydroxy vitamin D, converting vitamin D to its active form (1,25-dihydroxy vitamin D). This activated form of vitamin D increases the absorption of calcium (as Ca2+ ions) by the intestine via calbindin. (wikipedia.org)
  • kidney's
  • Co-first authors of the study Kimberly Homan, Ph.D., a Wyss Research Associate, and David Kolesky, Ph.D., a Wyss Postdoctoral Fellow, stress that the most exciting aspect of the work is that - far beyond mimicking the form of the kidney's proximal tubule - it is a credible in vitro model that functions like living kidney tissue, representing a significant advance from traditional 2D cell culture. (harvard.edu)
  • Type IV renal tubular acidosis (aldosterone resistance of the kidney's tubules) Gordon's syndrome (pseudohypoaldosteronism type II) ("familial hypertension with hyperkalemia"), a rare genetic disorder caused by defective modulators of salt transporters, including the thiazide-sensitive Na-Cl cotransporter. (wikipedia.org)
  • chronic
  • Kidney transplant is known to be the first choice therapy for end stage chronic kidney disease, also for its positive effects on kidney transplant recipients cardiovascular morbidity and mortality. (bioportfolio.com)
  • Indeed, advances in biomarker discovery and a greater appreciation of tubulointerstitial histopathology and the role of tubular hypoxia in the pathogenesis of chronic kidney disease have given us pause to reconsider the current "glomerulocentric" paradigm and focus attention on the proximal tubule that by virtue of the high energy requirements and reliance on aerobic metabolism render it particularly susceptible to the derangements of the diabetic state. (diabetesjournals.org)
  • urea
  • In the process of filtration, the kidneys retain as much water, sugars and salts as possible while filtering out the waste products, such as urea, states the Kidney & Urology Foundation of America. (reference.com)
  • Urea damages living tissues so, to cope with this problem, some fish retain trimethylamine oxide. (wikipedia.org)
  • lateral
  • In vertebrates, tight junctions (TJs) are found at the apical-most portion of the lateral surfaces, where the TJs form barriers both between the apical and basolateral surfaces and between adjacent cells, limiting paracellular permeability 7 ( FIG. 1a ). (pubmedcentralcanada.ca)
  • glomerular
  • These findings are, however, juxtaposed with the more recent knowledge that some patients with advanced disease display neither substantial glomerular pathology nor proteinuria and that kidney function declines well before traditional indicators of kidney disease such as microalbuminuria or creatinine-based estimated glomerular filtration rate (eGFR) decline ( 2 ). (diabetesjournals.org)
  • Moreover, the diabetes-induced injury to the proximal tubule may in turn lead to glomerular pathology and postglomerular hypoperfusion, while fibrotic expansion of the interstitium compresses and further disrupts the local microvasculature. (diabetesjournals.org)
  • Renal tubular acidosis (proximal type) (Fanconi syndrome) occurs when the PTECs are unable to properly reabsorb glomerular filtrate so that there is increased loss of bicarbonate, glucose, amino acids, and phosphate. (wikipedia.org)
  • Cells delivered into the renal artery showed initial glomerular localization with subsequent expansion into adjacent vasculature, interstitium, and tubules. (ufl.edu)
  • consists
  • Cubodial tissue is classified as simple, since it consists of only a single layer of cells, as reported by the University of Michigan Medical School. (reference.com)
  • occurs
  • In the intestine, via kidney, PTH enhances the absorption of calcium in the intestine by increasing the production of activated vitamin D. Vitamin D activation occurs in the kidney. (wikipedia.org)
  • subunit
  • In this video, see how the Wyss Institute team has advanced bioprinting to the point of being able to fabricate a functional subunit of a kidney, as reported in a new study published in Scientific Reports. (harvard.edu)
  • Therefore, the bioprinted 3D renal architecture recapitulates a very small - yet critical - subunit of a whole kidney. (harvard.edu)
  • While thus far we have merely demonstrated a functioning subunit within the kidney, we are actively scaling up the method and its complexity to enable future in vivo applications. (harvard.edu)
  • differentiate
  • Examining the ability of these cells to proliferate and differentiate in a whole kidney extracellular matrix scaffold would serve as a valuable baseline for future studies in producing a functioning organ. (ufl.edu)
  • After injury, mature terminally differentiated kidney cells dedifferentiate into more primordial versions of themselves and then differentiate into the cell types needing replacement in the damaged tissue Macrophages can self-renew by local proliferation of mature differentiated cells. (wikipedia.org)
  • cellular
  • Agonal resorption of the proximal tubular contents after interruption of circulation in the capillaries surrounding the tubule often leads to disturbance of the cellular morphology of the proximal tubule cells, including the ejection of cell nuclei into the tubule lumen. (wikipedia.org)
  • The evidence of cellular change of mouse stem cells in response to a rat scaffold is a promising step toward establishment of a xenogenic scaffold source for engineered kidneys. (ufl.edu)
  • concentration
  • PTH essentially acts to increase the concentration of calcium in the blood by acting upon the parathyroid hormone 1 receptor, which is present at high levels in bone and kidney, and the parathyroid hormone 2 receptor, which is present at high levels in the central nervous system, pancreas, testis, and placenta. (wikipedia.org)
  • structures
  • A diverse array of tissue structures and shapes can be formed by organizing groups of cells into different polarized arrangements and by coordinating their polarity in space and time. (pubmedcentralcanada.ca)
  • We discuss how conserved polarity complexes, signalling networks, transcription factors, membrane-trafficking pathways, mechanisms for forming lumens in tubes and other hollow structures, and transitions between different types of polarity, such as between epithelial and mesenchymal cells, are used in similar and iterative manners to build all tissues. (pubmedcentralcanada.ca)
  • functional
  • The current work further expands our bioprinting platform to create functional human tissue architectures with both technological and clinical relevance," said Lewis, who is also the Hansjörg Wyss Professor of Biologically Inspired Engineering at the Harvard John A. Paulson School of Engineering and Applied Sciences. (harvard.edu)
  • The use of functional tissue-like models during pre-clinical studies will provide unprecedented insights into human-relevant drug response prior to clinical development," said Moisan, a Laboratory Head in Mechanistic Safety at Roche and author of this study. (harvard.edu)
  • Human proximal tubule cells adhere to the hollow channel, forming a functional, 3D renal architecture. (harvard.edu)
  • commonly
  • This study will see how these two commonly used treatments (Everolimus and Panobinostat) work together in treating kidney cancer. (bioportfolio.com)
  • stem cells
  • Stem cells sourced from the adult kidney have the potential benefits of improved renal engraftment and differentiation and can be utilized in autologous therapies. (biomedcentral.com)
  • The field has aquired a good general base of knowledge, but scrutiny of the techniques and outcomes will be necessary to move toward a unified explanation of renal regeneration and the role of organ-specific stem cells in the kidney. (biomedcentral.com)
  • Pluripotent embryonic stem cells are highly proliferative, capable of differentiating into all cells of the kidney, and respond to tissue-specific extracellular matrix proteins. (ufl.edu)
  • cells
  • This work builds upon their demonstrated ability to bioprint tissue constructs composed of multiple types of living cells patterned alongside a vascular network in an extracellular matrix. (harvard.edu)
  • Lewis' team achieved this advance by adapting their earlier approach for bioprinting living cells to form thick tissues. (harvard.edu)
  • Although almost every eukaryotic cell is spatially asymmetric or polarized, polarity must be coordinated in space and time for individual cells to form a tissue 1 . (pubmedcentralcanada.ca)
  • the emergent properties of the tissue result from the combined roles of the individual cells that are involved. (pubmedcentralcanada.ca)
  • In newts, muscle tissue is regenerated from specialized muscle cells that dedifferentiate and forget the type of cell they had been. (wikipedia.org)
  • disease
  • The purpose of this study is to determine the disease processes that cause transplanted kidney dysfunctio. (bioportfolio.com)
  • Physicians taking a medical history may focus on kidney disease, medication use (e.g. potassium-sparing diuretics), which are common causes. (wikipedia.org)
  • In consequence, PTH is vital to health, and health problems that yield too little or too much PTH (such as hypoparathyroidism, hyperparathyroidism, or paraneoplastic syndromes) can wreak havoc in the form of bone disease, hypocalcaemia, and hypercalcaemia. (wikipedia.org)
  • organ-specific
  • Members of the claudin protein family, such as CLDN2, are expressed in an organ-specific manner and regulate the tissue-specific physiologic properties of tight junctions (Sakaguchi et al. (wikipedia.org)
  • circulation
  • A third important effect of PTH on the kidney is its stimulation of the conversion of 25-hydroxy vitamin D into 1,25-dihydroxy vitamin D (calcitriol), which is released into the circulation. (wikipedia.org)
  • found
  • In 1895 Thomas Morgan removed one of a frog's two blastomeres and found that amphibians are able to form whole embryos from the remaining part. (wikipedia.org)
  • whole
  • Decellularization of whole rat kidneys was achieved by perfusion of detergent-based solutions through the renal artery. (ufl.edu)
  • process
  • Parathyroid hormone (PTH), also called parathormone or parathyrin, is a hormone secreted by the parathyroid glands that is important in bone remodeling, which is an ongoing process in which bone tissue is alternately resorbed and rebuilt over time. (wikipedia.org)
  • Long
  • A strongly positive crossmatch has long been considered an absolute contraindication to kidney transplantation and most patients with anti-HLA antibody never were able to receive a kidney transplant. (bioportfolio.com)
  • distinct
  • Cytosolic and membrane-bound forms of glutathione S-transferase are encoded by two distinct supergene families. (wikipedia.org)
  • often
  • The tubules, often referred to as the renal tubules, reabsorb the beneficial solutes and water back into the body while continuing the filtration of the waste during its journey to the bladder. (reference.com)
  • testis
  • PTH essentially acts to increase the concentration of calcium in the blood by acting upon the parathyroid hormone 1 receptor, which is present at high levels in bone and kidney, and the parathyroid hormone 2 receptor, which is present at high levels in the central nervous system, pancreas, testis, and placenta. (wikipedia.org)
  • necrosis
  • Kidneys were harvested for histopathology and for the study the gene expression of c-Jun N-terminal kinases ( JNK ), Mitogen-activated protein kinase 4 ( MKK4 ), MKK7 , P38 mitogen-activated protein kinases ( P38 ), tumor necrosis factors alpha ( TNF-α ), TNF Receptor-Associated Factor 2 ( TRAF2 ), and interleukin-1 alpha ( IL-1-α ). (biomedcentral.com)
  • absorption
  • In the intestine, via kidney, PTH enhances the absorption of calcium in the intestine by increasing the production of activated vitamin D. Vitamin D activation occurs in the kidney. (wikipedia.org)
  • PTH up-regulates 25-hydroxyvitamin D3 1-alpha-hydroxylase, the enzyme responsible for 1-alpha hydroxylation of 25-hydroxy vitamin D, converting vitamin D to its active form (1,25-dihydroxy vitamin D). This activated form of vitamin D increases the absorption of calcium (as Ca2+ ions) by the intestine via calbindin. (wikipedia.org)
  • bone
  • Parathyroid hormone (PTH), also called parathormone or parathyrin, is a hormone secreted by the parathyroid glands that is important in bone remodeling, which is an ongoing process in which bone tissue is alternately resorbed and rebuilt over time. (wikipedia.org)
  • In consequence, PTH is vital to health, and health problems that yield too little or too much PTH (such as hypoparathyroidism, hyperparathyroidism, or paraneoplastic syndromes) can wreak havoc in the form of bone disease, hypocalcaemia, and hypercalcaemia. (wikipedia.org)
  • Parathyroid hormone regulates serum calcium through its effects on bone, kidney, and the intestine: In bone, PTH enhances the release of calcium from the large reservoir contained in the bones. (wikipedia.org)
  • The binding of RANKL to RANK (facilitated by the decreased amount of OPG available for binding the excess RANKL) stimulates these osteoclast precursors to fuse, forming new osteoclasts, which ultimately enhances bone resorption. (wikipedia.org)
  • serum
  • The cisplatin single dose administration to rats induced nephrotoxicity associated with a significant increase in blood urea nitrogen (BUN) and serum creatinine and significantly increase Malondialdehyde (MDA) in kidney tissues by 230 ± 5.5 nmol/g compared to control group. (biomedcentral.com)
  • injury
  • After injury, mature terminally differentiated kidney cells dedifferentiate into more primordial versions of themselves and then differentiate into the cell types needing replacement in the damaged tissue Macrophages can self-renew by local proliferation of mature differentiated cells. (wikipedia.org)
  • certain
  • 53 Hartnup disease is a metabolic disorder characterized by abnormal transport of certain amino acids in the kidney and gastrointestinal system. (malacards.org)
  • important
  • In terrestrial animals, such as reptiles, birds and mammals, the kidneys are important osmoregulatory structures. (biologyboom.com)
  • A third important effect of PTH on the kidney is its stimulation of the conversion of 25-hydroxy vitamin D into 1,25-dihydroxy vitamin D (calcitriol), which is released into the circulation. (wikipedia.org)
  • active
  • This latter form of vitamin D is the active hormone which stimulates calcium uptake from the intestine. (wikipedia.org)
  • expression
  • The AGE- and CML-dependent activation of NF-κBp65 and NF-κB-dependent IL-6 expression could be inhibited using the soluble form of the receptor for AGEs (RAGE) (soluble RAGE [sRAGE]), RAGE-specific antibody, or the antioxidant thioctic acid. (diabetesjournals.org)
  • water
  • Plants share with animals the problems of obtaining water but, unlike in animals, the loss of water in plants is crucial to create a driving force to move nutrients from the soil to tissues. (wikipedia.org)
  • Succulent plants such as the cacti store water in the vacuoles of large parenchyma tissues. (wikipedia.org)