Kidney transplantation is a potentially life-saving treatment option for patients with chronic kidney disease, but every year thousands of patients die while on the organ waiting list. To address this problem, scientists have turned to the development of bioartificial kidneys — devices that use human kidney cells and hollow fiber membranes to fulfill the various functions of a normal human kidney.
Clinical studies have demonstrated the safety of bioartificial kidneys. However, the technology still has some weaknesses — for example, the clogging of membrane pores, which can lower the performance of the bioartificial kidney, and the incompatibility between the membrane material and human kidney cells.
A team of researchers led by Daniele Zink and Jackie Ying at the A*STAR Institute of Bioengineering and Nanotechnology have now developed a coating that promotes the growth and differentiation of human kidney cells on hollow fiber membranes. In addition, they have proposed a membrane morphology that could prevent pores from clogging.
A bioartificial kidney typically consists of a hemofilter, which is used to remove waste from the bloodstream, and a bioreactor, which houses human kidney cells for performing various kidney functions.
Most of the hollow fiber membranes found on the market are optimized for use in hemofilters. They are typically smooth and nanoporoous on the inside (the side exposed to blood) and have relatively large pores on the outside. Zink, Ying and co-workers examined the performance of such membrane design under conditions as applied in the bioreactor unit and found that the pores were clogged by a build-up of proteins. Because of this, the researchers recommended the use of an alternative membrane design that is more suited for bioreactors — one that is smooth on the outside and has the larger pores on the inside.
Because primary human kidney cells do not grow and survive well on most polymer membranes, the researchers coated the inner surface of their hollow fibers with 3,4-dihydroxy-L-phenylalanine, or DOPA, and collagen to stimulate cell proliferation and differentiation. Cell behavior studies showed that most cells in the bioreactor expressed the appropriate differentiation marker proteins for human kidney cells.
And because primary human kidney cells are expensive and only available in limited quantities, the researchers developed a bioreactor comprising a single hollow fiber. The new apparatus could test for the performance of human kidney cells that are limited in numbers.
The researchers have so far only tested the performance of their hollow fiber membranes in bioreactors with primary human kidney cells. “Kidney cells derived from stem cells are a better alternative as there is an unlimited supply and there are no issues of interdonor variability,” says Zink. “We are now investigating how human kidney cells derived from stem cells perform under bioreactor conditions.”
The A*STAR-affiliated researchers contributing to this research are from the Institute of Bioengineering and Nanotechnology.