A kidney-like organ grown from scratch in the lab has been shown to work in animals – an achievement that could be the prelude to growing spare kidneys for someone from their own stem cells.
Donated kidneys are in huge demand worldwide. In the UK alone, there are7200 people on the waiting list – a state of affairs that the new study takes a small step towards ending.
Christodoulos Xinaris of the Mario Negri Institute for Pharmacological Research in Bergamo, Italy, and his colleagues extracted cells from the kidneys of mouse embryos as they grew in the mother. The cells formed clumps that could be grown for a week in the lab to become "organoids" containing the fine plumbing of nephrons – the basic functional unit of the kidney. A human kidney can contain over 1 million nephrons.
Chemical broth
Next, Xinaris's team marinated the organoids in a chemical broth called vascular endothelial growth factor (VEGF), which makes blood vessels grow. Then they transplanted the organoids onto the kidneys of adult rats.
By injecting the rats with extra VEGF, the researchers encouraged the new tissue to grow its own blood vessels within days. The tissue also developed features called glomeruli, chambers where blood enters the nephrons to be cleansed and filtered.
The researchers then injected the animals with albumin proteins labelled with markers that give out light. They found that the kidney grafts successfully filtered the proteins from the bloodstream, proving that they could crudely perform the main function of real kidneys.
"This is the first kidney tissue in the world totally made from single cells," says Xinaris. "We have functional, viable, vascularised tissue, able to filter blood and absorb large molecules from it. The final aim is to construct human tissues."
"The ability to build functional renal tissue starting from suspensions of single cells represents a considerable step toward the practical goal of engineering renal tissues suitable for transplantation and offers the methodological basis for a number of investigative and therapeutic applications," said Dr. Xinaris. For example, disease-related genes could be introduced into an organoid to help researchers study the mechanisms of complex kidney diseases and to perform a preliminary screening of new drugs to treat them.
Study co-authors include Valentina Benedetti, BiolSciD, Paola Rizzo, BiolSciD, Mauro Abbate, MD, Daniela Corna, Nadia Azzolini, Sara Conti, BSc, Mathieu Unbekand, PhD, Jamie A. Davies, PhD, Marina Morigi PhD, Ariela Benigni, PhD, and Giuseppe Remuzzi, MD.
In Vivo Maturation of Functional Renal Organoids Formed from Embryonic Cell Suspensions
- Christodoulos Xinaris*,
- Valentina Benedetti*,
- Paola Rizzo*,
- Mauro Abbate*,
- Daniela Corna*,
- Nadia Azzollini*,
- Sara Conti*,
- Mathieu Unbekandt†,
- Jamie A. Davies†,
- Marina Morigi*,
- Ariela Benigni*and
- Giuseppe Remuzzi*‡
+Author Affiliations
- Correspondence:
Dr. Christodoulos Xinaris, “Mario Negri” Institute for Pharmacological Research, Centro Anna Maria Astori, Science and Technology Park Kilometro Rosso, Via Stezzano 87, 24126 Bergamo, Italy. Email: christodoulos.xinaris@marionegri.it
- Received for publication May 21, 2012.
- Accepted for publication July 26, 2012.
Abstract
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.
- Copyright © 2012 by the American Society of Nephrology
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