Researchers at Brigham & Women’s Hospital (BWH) and Harvard Stem Cell Institute (HSCI) have used skin-derived stem cells to develop kidney organoids. These structures can be used to study various kidney diseases, development, drug toxicity, and kidney injury. Eventually, this technology could be used to create kidney tissues that function within the patient, decreasing or even eradicating the need for kidney transplants.
These structures can be used to study various kidney diseases, development, drug toxicity, and kidney injury.
The human kidney includes almost 2 million nephrons, which are responsible for filtering the blood. This filtration system is necessary for excretion of waste and control of the body’s pH, electrolyte balance, and hydration.
Current treatments for kidney failure patients include dialysis and kidney transplantation, which are both costly and potentially harmful. There is also a greater demand than supply of kidneys available for transplant.
When cultured, the human-pluripotent-stem-cell-derived kidney cells (HPSC-KCs) form spheroids around hollow cavities, which then differentiate into segmented, nephron-like kidney organoids. These organoids include structures of tubules, podocytes and endothelium as seen in the human kidney.
The development of these structures can be analyzed for a better understanding of kidney diseases. Diseased organoids can be developed and then used as models to work towards therapies. For example, knockouts of polycystic kidney disease genes PKD1 or PKD2 cause cysts to form within the tubule structures of the organoids.
The gene mutations associated with polycystic kidney disease and glomerulonephritis were among the first mutations introduced into healthy hPSC-KCs. Using CRISPR technology in combination with the kidney organoids, BWH and HSCI are now creating disease models. CRIPSR/Cas9 system is a gene editing method that comes from the prokaryotic immune system. The Cas9 endonuclease enzyme and guide RNA cut the genome of an organism at a specific location. This technology is being investigated as treatment for genetic diseases and for the creation of disease models.
Using CRISPR technology in combination with the kidney organoids, BWH and HSCI are now creating disease models.
Kidney organoids provide a large amount of information about the kidneys and potential therapies for kidney diseases, as well as opportunities for an increased speed of research and drug testing. Lastly, they reveal that many organ structures and human diseases can be recreated in the lab, highlighting their potential for use in research and for the development of treatments.
Freedman, Benjamin S. et al. (2015, Oct 23). Modelling kidney disease with CRISPR- mutant kidney organoids derived from human pluripotent epiblast spheroids. Nature Communications. Retrieved fromhttp://www.nature.com/ncomms/2015/151023/ncomms9715/pdf/ncoms9715.pdf
Takasato, Minoru et al. (2015, Oct 7). Kidney organoids from human iPS cells contain multiple lineages and model human nephrogenesis. Nature. Retrieved from http://www.nature.com/nature/journal/v526/n7574/pdf/nature15695.pdf