The Engineering of Kidney Organoids Proceeds Apace

This is the organoid era of tissue engineering. Researchers are making earnest progress in establishing the recipes that allow cells to be grown into small, functional tissue sections. They lack a network of capillaries, however, so must be no more than a millimeter or so in thickness in order for nutrients to perfuse sufficiently through the tissue to support all of its cells. Every organ, every tissue has a significantly different recipe, but it is usually something that can be derived from an examination of the biochemistry of embryonic growth, with enough time and funding. Given the large number of different tissues versus the smaller number of research groups working on tissue engineering, this process of discovery will be going on for a while yet. It has taken a great deal of time and effort to produce the first functional organoids, and it will take longer yet to manage complete coverage of the human body.

Today I'll point out a couple of recent articles that focus on kidney organoids specifically. Kidney function is not independent of structure and location as is the case for the liver, so one can't just put kidney organoids into a patient's lymph nodes, as Lygenesis is doing with liver sections. It is nonetheless plausible to transplant some number of kidney organoids into a failing kidney and have them integrate usefully to support overall kidney function. It may be the case that this becomes a widespread mode of therapy before a reliable solution is found for construction of capillary networks in engineered tissue, a challenge that presently blocks the way towards building larger tissue sections and whole organs from a patient's own cells. Or it may not; the future is hard to predict at the best of times, never mind when the research is moving as fast as it is these days.

Engineered mini-kidneys come of age

With organs-in-a-dish a growing success story, research with organoids has increasingly proved its worth. Already, scientists can create organoids that have many of the cell types and complex architectures of human organs such as the kidney, liver, guts, and even the brain. Most organoids grown in vitro, however, have lacked the vasculature to provide the cells with oxygen and nutrients, remove metabolic waste, and facilitate communication between cell types - functions that drive their maturation into working tissue-building blocks.

When it comes to kidney organoids, that shortcoming has kept researchers from reproducing key functions, such as blood filtration, reabsorption, and urine production. A vascularized organoid could better model kidney diseases, enhance renal drug toxicity testing, and ultimately lead to building blocks for replacement therapies. To answer that need, a team of researchers has developed a powerful new approach. By exposing stem cell-derived organoids to fluidic shear stress, they have significantly expanded their vascular networks and improved the maturation of kidney compartments. They hypothesized that fluid flow could help the models form blood vessels from precursor endothelial cells found in growing kidney organoids - and successfully, for the first time, demonstrated that by exposing the organoids to fluid flow, their vascularization and maturation can be enhanced in vitro, rather than in an animal host.

"The vascular networks form close to the epithelial structures that build the glomerular and tubular compartments, and in turn promote epithelial maturation. This integrated process works really like a two-way street. Our method may pave the way to also vascularize other types of organoids, such as the liver organoids."

Researchers develop mini kidneys from urine cells

Thanks to revolutionary developments in stem cell research, scientists can grow mini intestines, livers, lungs and pancreases in the lab. Recently, by growing so-called pluripotent stem cells, they have also been able to do this for kidneys. In a study, researchers used adult stem cells, directly from the patient, for the first time. Cells from urine also proved to be ideal for this purpose. A mini kidney from the lab doesn't look like a normal kidney. But the simple cell structures share many of the characteristics of real kidneys, so researchers can use them to study certain kidney diseases.

"We can use these mini kidneys to model various disorders: hereditary kidney diseases, infections, and cancer. This allows us to study in detail what exactly is going wrong. This helps us to understand the workings of healthy kidneys better, and hopefully, in the future, we will be able to develop treatments for kidney disorders. In the lab, we can give a mini kidney a viral infection which some patients contract following a kidney transplant. We can then establish whether this infection can be cured using a specific drug. And we can also use mini kidneys created from the tissue of a patient with kidney cancer to study cancer."

Comments

Given all the progress we witness with stem cells and organoïds it is baffling that we didn't still solve the vascularizaiton problem yet. At the extreme one can decellularize a teratoma and stitch it to an organoid...

Posted by: cuberat at March 12th, 2019 4:23 PM

Off topic, but I haven't seen any mention here of De Grey's recent announcement that he's updated his timeframe estimate as concerns the arrival of Robust Mouse Rejuvenation. He's now saying that due to recent advances, and senolytics in particular, he thinks there's a fifty/fifty chance of RMR within three years.

https://www.youtube.com/watch?v=PMFST20xHwk

Posted by: Ben at March 12th, 2019 10:32 PM

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