October 19, 2015
2015 may be considered The Year of the Lab-Grown Organ. Multiple investigators have bio-engineered sophisticated and advanced organoid models from human cells to replicate the function and anatomy of the brain, heart, and liver, among others. But the kidneys have presented special challenges.
The kidney is especially important in drug development due to its role in filtering waste products from the blood. It is a common site for toxicity due to drugs.
Animal experiments are typically used to evaluate a drug’s effect on the kidneys. In addition to the immense suffering that causes, results from animals are inaccurate for over 92% of drugs tested.
Now, a new breakthrough in lab-grown organs can hasten the transition away from animal tests for renal toxicity. Two independent teams of scientists in the U.S. and Australia have created mini-kidney models by re-engineering human stem cells into renal tissue that can function at a rudimentary level as a mature kidney. Both teams developed the kidney organoids from adult stem cells derived from skin tissue.
A mini-kidney in a dish generated from human pluripotent stem cells.
The three colors show the presence of distinct cell types.
Photo Credit M. Takasato, Murdoch Institute
The Australian team led by Dr. Melissa Little of the Murdoch Children's Research Institute in Melbourne, utilized natural cell growth factors that directed the engineered cells to spontaneously form into the full array of cell types found in the human kidney, including blood vessels, connective tissue and nephrons – the small ducts that are vital to the kidney’s functional anatomy.
The specialized cells allow the mini-organ to filter blood and assist with fluid and electrolyte balance, essential functions of the mature kidney.
In the U.S. scientists at Brigham and Women’s Hospital (BWH) and the Harvard Stem Cell Institute (HSCI) also devised a novel process to convert adult stem cells into kidney cells that self-assembled into an organoid resembling a human kidney.
Kidney organoid from iPCs modeling kidney development
Photo credit: R.Morizane, Harvard
The Australian team tested the kidney organoid for its response to cisplatin, a powerful anti-cancer drug that can affect the kidneys, and demonstrated that it showed similar damage to what is seen in the mature kidney.
The ultimate goal is to develop a transplantable organ. Until then, both research teams believe the kidney organoids will aid in drug development by screening drugs for renal toxicity.
Dr. Jamie Davies, an anatomy professor at the University of Edinburgh who was not involved in the research, wrote in Nature that the kidney organoid may provide “the ability to test drug safety on human kidney tissue, rather than in poorly predictive animals.”
“The result could be a major step towards animal replacement and improved safety screening for drugs, as well as towards transplantable kidneys.”
Both research teams believe the mini-kidney opens the door for other therapies to treat kidney disease. Perhaps most importantly, scientists can use a patient’s own cells to create a personalized model to test treatments specific to that patient.
“This approach is especially attractive because the tissues obtained would be ‘personalized’ and, because of their genetic identity to the patient from whom they were derived, this approach may ultimately lead to tissue replacement without the need for suppression of the immune system,” said Joseph V. Bonventre, chief of BWH’s Renal Division and Chief of BWH’s Division of Biomedical Engineering.
For years scientists have attempted to genetically modify animals, typically pigs and monkeys, to use their organs for transplants. These efforts continue despite having consistently failed and consumed the lives of thousands of animals.
Kidney disease is on the rise, and with it, the shortage of suitable organs for transplant. Working with human cells and tissues to generate organs that are 100% biologically compatible, the emerging field of regenerative medicine is the most realistic, humane and scientifically sound approach to the problem.
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