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Advancements In Renal Regeneration

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Robina Weermeijer/Unsplash

The complexity of the renal system has made regenerating it a challenge to the scientific community, leaving it behind compared to the regeneration advancements of other organ systems.

By Patrick James Hibbert 
24 JUn 2019

Organ regeneration with stem cells may be the solution for thousands of patients on donor lists according to Kidney.org. The National Institute of Diabetes and Digestive and Kidney Diseases located, in Bethesda, Maryland, leads a consortium called "(Re)building a Kidney". Their goal is to advance isolation, expansion, and differentiation techniques used in the integration of kidney cells into viable structures that replicate human kidney function.

Scientists from Tokyo, Japan published a study in the scientific journal F1000 on the advancements made in the field of renal regeneration made thus far. They say that recent technological advances in human regenerative medicine can help in regenerating the complex spatial arrangement of kidneys. 

They go on to say, to create a functional kidney 3 types of progenitor cells must be induced: nephron progenitors, a ureteric bud, and stromal progenitors. However, only 2 of the 3 can be accomplished with today’s technology, they can create all of them except the stromal progenitors.

There are other renal regeneration techniques being used nonetheless. In fact, scientists use many processes today in labs to generate renal organs. One of them involves decellularizing kidneys to yield acellular scaffolds. This process has been performed successfully on rats. They use these scaffolds to add epithelial and endothelial cells to before processing them in whole-organ bioreactors. Kidneys created this way have excretory functions once transplanted in rats but more research and development is needed before it can be used clinically. 

Another method, called three-dimensional (3D) bio-printing, combines cells, growth factors, and biomaterials to make biomedical parts that imitate natural tissues, but does so however with their physiological functions missing. Scientists have used this method to successfully reconstructed the structures of proximal tubules and vasculatures. 

Stem cell regeneration has been used by scientists to grow organs. Although, because of the complex structure of a functional kidney, regenerating it from pluripotent stem cells, those that can develop into any type of cell or tissue, is challenging. 



Renal-Progenitors
The Three Renal Progenitors In The Kidney: Stromal, Nephron, and Ureteric Bud

  • Ureteric bud and stromal progenitors work together to develop the kidney organ. 
  • Ureteric bud tips send Wnt signals to maintain and induce the transition of the nephron progenitors from the mesenchyma to the epithelial layer.
  • Nephron progenitors produce a protein called glial cell-derived neurotrophic factor (Gdnf) to maintain ureteric bud tip proliferation.
  • Stromal progenitors send retinoic acid (RA) signals to support ureteric branching. 

Kidneys have been successfully regenerated in other species though. Notably, rat-derived nephrons were regenerated in mice by combining their nephron progenitors. Today, this feat serves as a demonstration and a platform for regenerating kidneys in other species. Similarly, rat embryonic kidneys and bladders were developed from cloacas, which were then transplanted into a host rat, creating a stepwise peristaltic ureter system. 

On the whole, the advancements in renal regeneration are falling behind in terms of technology compared with the regeneration of other organs. So far, producing nephron progenitors from human induced pluripotent stem cells, regenerating human nephrons in other species, and constructing a urinary excretion pathway – the most promising strategy – are the three ways, theoretically and only when combined together that, functional kidneys can be reconstructed. 

There are many reasons renal regeneration would be beneficial in light of the system’s many pathologies. Congenital defects, obstructions, infections, inflammations, vascular disorders, and chronic failures are common ones.

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