In Vivo Maturation of Functional Renal Organoids Formed from Embryonic Cell Suspensions

The shortage of transplantable organs provides an impetus to develop tissue-engineered alternatives. Producing tissues similar to immature kidneys from simple suspensions of fully dissociated embryonic renal cells is possible in vitro, but glomeruli do not form in the avascular environment. Here, we...

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Bibliographic Details
Published inJournal of the American Society of Nephrology Vol. 23; no. 11; pp. 1857 - 1868
Main Authors XINARIS, Christodoulos, BENEDETTI, Valentina, BENIGNI, Ariela, REMUZZI, Giuseppe, RIZZO, Paola, ABBATE, Mauro, CORNA, Daniela, AZZOLLINI, Nadia, CONTI, Sara, UNBEKANDT, Mathieu, DAVIES, Jamie A, MORIGI, Marina
Format Journal Article
LanguageEnglish
Published Washington, DC American Society of Nephrology 01.11.2012
Subjects
Animals
Basic Research
Bioartificial Organs
Biological and medical sciences
Kidney - blood supply
Kidney - cytology
Kidney - embryology
Kidney - physiology
Kidney Transplantation - methods
Male
Medical sciences
Mice
Nephrology. Urinary tract diseases
Organoids - cytology
Organoids - embryology
Organoids - transplantation
Rats
Rats, Nude
Tissue Engineering - methods
Transplantation, Heterologous
Vascular Endothelial Growth Factor A - administration & dosage
In vivo
Nephrology
Urinary system
Embryonic cell
Suspension
Kidney
Urology
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Summary:The shortage of transplantable organs provides an impetus to develop tissue-engineered alternatives. Producing tissues similar to immature kidneys from simple suspensions of fully dissociated embryonic renal cells is possible in vitro, but glomeruli do not form in the avascular environment. Here, we constructed renal organoids from single-cell suspensions derived from E11.5 kidneys and then implanted these organoids below the kidney capsule of a living rat host. This implantation resulted in further maturation of kidney tissue, formation of vascularized glomeruli with fully differentiated capillary walls, including the slit diaphragm, and appearance of erythropoietin-producing cells. The implanted tissue exhibited physiologic functions, including tubular reabsorption of macromolecules, that gained access to the tubular lumen on glomerular filtration. The ability to generate vascularized nephrons from single-cell suspensions marks a significant step to the long-term goal of replacing renal function by a tissue-engineered kidney.
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ISSN:1046-6673
1533-3450
DOI:10.1681/asn.2012050505