Tissue Engineering of Better, More Correctly Structured Kidney Organoids

The research community continues to improve their ability to build structured and functional organ tissue from the starting point of a patient cell sample. The challenge of constructing blood vessel networks to support large tissue structures remains to be solved, but by the time it is, there will be a direct path to the manufacture of entire organs on demand. Work on kidney tissue is one of the leading areas from the point of view of technical capabilities in tissue engineering, as this research news demonstrates.

In the embryonic kidney, three types of precursor cells, nephron progenitor cells, ureteric buds, and interstitial progenitor cells, interact to form three-dimensional structures of the kidney. Methods to induce nephron structures via nephron progenitor cells from mouse pluripotent stem cells (PSCs) have already been established. However, since other progenitor cells were not included, the "higher-order" structures of the kidney (the state in which differentiated nephron structures are organically connected to each other by branching collecting ducts) were not reproduced. Now, a research group has developed a method of using PSCs to induce production of ureteric buds, the progenitors of branched collecting ducts, and has succeeded in reproducing the higher-order structure of the kidney.

Unfortunately, opportunities for kidney transplantation are limited, but the 2006 discovery of induced pluripotent stem cells (iPS cells) has elevated the expectation for regenerative medicine to "build" fully functioning organs. However, the process of reproducing a whole organ structure continues to be a common and challenging theme for any organ regeneration study. Researchers are working toward the goal of producing a fully functional kidney. To do so, it is important to reconstruct higher-order kidney structures from PSCs.

The researchers first discovered that mouse Wolffian ducts (WDs), precursors of ureteric buds, gradually matured and gained branching capacity between embryogenesis day (E) 8.75 and E11.5. They were then able to culture WD cells in vitro and determined the growth factors necessary to produce mature ureteric buds. Finally, they developed a protocol to induce E11.5 ureteric bud-like cells from mouse ESCs via E8.75 WD-like cells. It was revealed here that nephron progenitor cells and ureteric buds require individually optimized conditions for successful induction.

Functionality of mouse ESC-derived ureteric buds was further verified by co-culturing a single bud with embryonic kidney precursors, or with a mixture of ESC-derived nephron progenitors and embryonic stromal progenitors. In the reconstructed kidney organoid, researchers observed the formation of branching ureteric epithelium, differentiated nephrons, and nephron progenitors on the surface of the ureteric bud tips, thereby confirming the functionality of induced ureteric buds and the reconstruction of higher-order kidney structures. With a slight modification of the protocol, the researchers were able to induce ureteric buds from human iPSCs, and confirmed their branching capacity when cultured with growth factors.

Link: https://www.eurekalert.org/pub_releases/2017-12/ku-rhe121817.php


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