Ever since I learned the solution to the old chicken and egg paradox, I have stopped using that phrase to describe a scenario where it is difficult to determine the order of two events. According to evolutionary geneticists, the egg always comes first—a chicken-like creature laid an egg that had a genetic mutation, so when the egg hatched, a chicken-little came out. So because of those geneticists, I can no longer use that expression. But that is not the only expression that faces extinction: in the near future, I fear we can no longer say, “I can afford X only if I sell my kidney.” Thanks to some recent advances in stem cell research, our kidneys may not be as valuable as we think them to be in the future. How could we compete if human kidneys could be mass produced in a laboratory? Yes, we have some time before that happens, but a functional, artificial kidney may come out much earlier than we think. A recent paper by Atsuhiro Taguchi and Ryuichi Nishinakamura (Cell Stem Cell, December 2017) highlights the advances that have been made in artificial organ development.
The story begins with pluripotent stem cells (PSCs). These cells can be converted to just about any other cell types under appropriate condition (the term pluripotency comes from Latin that means the ability for many). In this paper, the authors generated two main precursors of a kidney from PSCs: nephron progenitors (NP) and the ureteric bud (UB). Sounds simple, but how did they know under what condition(s), the PSCs would give rise to those two different cell types?
To find out the cues that give rise to these cells, the authors looked carefully at the kidney development in mice. They found that slight differences in particular signaling affected the conversion dynamics of these two cell types. This finding suggested the possibility to covert PSCs into NP and UB cells by modulating that signaling. Based on this, the researchers eventually identified and optimized the conditions that could convert PSCs into NP and UB cells. Other labs now can use their protocol and make those two cell types from PSCs. But what about making the actual kidney with these two cells types?
It turns out that to make a functional, embryonic kidney, the researchers needed another cells type, the Stromal Progenitors (SP). Since they could not generate these SP cells from PSCs, they took SP cells from mice and then grew these three cell types (NP, UB, and SP) together in a culture dish for a week. After a week, these three cells gave rise to organoid kidneys: rudimentary and simplified kidneys. They then carefully inserted these organoids into embryonic mouse kidneys and observed the development of these organoids. The found that the reassembly of those three cell types not only mirrored physiological interaction among these cells but also created nephrons—the structural units of the kidney that are required for drainage/filtration.
Can the same technique be used to generate functional nephrons in humans? To address this question, the researchers generated human NPs and UBs using human PSCs and grew them in culture. While initially, the development of the organoid kidneys was similar to mice organoid culture, there was no further development after a week. Since the scientists did not have human SP cells, it is possible that only aggregation and reassembly of all three cell types can give rise to functional embryonic kidneys as observed in mice. It is also possible that human NPs and UBs have different characteristics and more studies are needed to sort that out. Furthermore, to develop kidney tissue reconstruction and ensure its proper maturation, the scientists most likely will need to integrate functional blood vessels and blood circulation system within the artificial embryonic kidney. So we still have to solve some technical problems and/or expand this current modular system before we can grow functional kidneys ready for a kidney transplant.
Still, as most of the organoids developed before this study fail to establish a proper connection between different cell types, the generation of functional nephrons is remarkable progress. When a fully functional artificial kidney will appear, I cannot say, but I predict it won’t be that long. In the meantime, unless you are desperate to buy a Porsche and selling your kidney is your only option, I suggest steering away from organ brokers because for now, we only have two of them.