Streaming fluid across kidney organoids—mini kidney-like structures—grown on a chip drives their maturation
Scientists found that streaming fluid across kidney organoids—engineered aggregations of kidney cells— prompts the organoids to develop blood vessels and to form natural tissue structures when grown on a chip, dramatically improving the extent to which they replicate normal kidney functions. Kidneys are highly complex organs in which systems of blood vessels intertwine with other structures to filter extra water and wastes out of the blood and make urine. Loss of kidney function can thus lead to build up of toxins in the blood and other problems, and total kidney failure is deadly without dialysis or a kidney transplant. Therefore, scientists have sought to develop treatments to repair, replace, or enhance lost kidney function. For many years, researchers have been improving methods to use human stem cells in the laboratory to engineer kidney organoids, which are three-dimensional tissue constructs that can mimic kidney functions. However, it has been challenging to integrate blood vessels into growing organoids and coax stem cells to take on the required properties of kidney cells, and researchers have sought ways to overcome these technological hurdles to generate mature kidney organoids that fully replicate kidney function.
In a recent study, researchers attempted to recreate some of the environmental conditions under which kidneys normally develop in the body to see if these conditions would help organoids to mature properly. The scientists mounted organoids to small platforms, or “chips,” that can be modified to test various technological parameters. They reasoned that because developing kidneys normally are exposed to a flow of surrounding fluids, perhaps adding the stress of fluid flow to these chips could better mimic the natural environment. When the researchers grew chip-mounted kidney organoids in the presence of a high rate of fluid flow, they developed an array of blood vessels with varying diameters; by contrast, organoids exposed to low fluid rate or none at all had far fewer blood vessels. These blood vessels infiltrated the organoids and connected with internal tissue structures, as is required for normal kidney functions. The scientists found that under high flow conditions, the developing blood vessels successfully transported fluids, and even assembled as networks connecting neighboring organoids. Organoids exposed to high flow also formed critical kidney tissue structures that closely resembled those found in normal kidneys. Together, these findings revealed that organoids grown on chips under high fluid flow conditions were far more physiologically mature than those under low or no flow.
The technological advances achieved in this study have boosted the ability of organoids on chips to mimic the natural physiological function of human kidneys. These conditions may help researchers utilize chips to test potential new drugs more quickly and accurately than has been possible. Improved kidney organoids also represent an important step toward the future development of functional, implantable structures that can enhance or replace lost kidney function in people.
Homan KA, Gupta N, Kroll KT,…Morizane R. Flow-enhanced vascularization and maturation of kidney organoids in vitro. Nat Methods 16: 255-262, 2019.