Genetic experimentation has made impressive advancements in the past 20 years. In 1996 the Nishinakamura laboratory began experimenting with Xenopus frogs because of its powerful combination of experimental tractability and close evolutionary relationship with humans. The animal cap, which is a small part of blastula stage Xenopus embryos, can be differentiated into several types of cells (ter med pluripotential) when exposed to the right inducers.
Three pairs of kidneys are developed during embryonic life. Two of the pairs of kidneys eventually atrophy and degenerate leaving only one pair of functioning kidneys. This complicates kidney generation strategies in vitro.
The pronephroi are rudimentary and nonfunctional kidney structures that begin to develop at the beginning of the fourth week and late in the fourth week they degenerate. The mesonephroi are the second set of kidneys to form late in the fourth week of embryonic life and stay functioning for about four weeks until they are replaced by the final pair of kidneys. The metanephroi eventually develop into the final and permanent kidneys. They begin to develop early in the fifth week of embryonic life but do not function until approximately four weeks later.
Another challenge is the development of the many complex structures and blood vessels normally present within the kidneys. Although it is possible to recreate the structures, they are not without flaws. The structural components of the kidney grown in vitro are still lacking when compared to the normal kidney.
Although these studies represent notable advances during the twenty years of intensive research, there are still areas of each component needing to be improved. The creation of a kidney in vitro, however, is no longer just a dream. Currently, it is possible to recapitulate the in vivo developmental processes in vitro using pluripotent stem cells. One can only imagine what will be possible in the next twenty years.
- Ryuichi Nishinakamura & Sazia Sharmin & Atsuhiro Taguchi. Induction of nephron progenitors and glomeruli from human pluripotent stem cells. Pediatr Nephrol (2017) 32:195–200.