Recent reports of laboratory-created rat kidneys provide hope for the future of bioengineered kidneys for those with kidney disease. Students can get involved in this hot area of biomedical technology and research with their own bioinformatics projects.
Many medical conditions involve treatment and therapy that have life-altering consequences, but for patients in renal failure, a condition in which the kidneys stop functioning, the feeling of being tied down has very literal significance. Patients with end-stage kidney disease often spend many hours, multiple times a week, hooked up to dialysis machines that do what their kidneys are no longer able to do—filter waste, salt, and extra water from the body. Dialysis also helps keep certain chemicals in the body in balance and works to keep a patient's blood pressure stable.
Though the treatment involves being tethered to giant machines for hours on end, for patients in renal failure, dialysis may be the only thing the keeping them alive. Many of these patients are waiting for a kidney transplant. Unfortunately, organ availability is far lower than the number of patients in need of a kidney.
Supply and Demand
Thousands of patients die each year while awaiting kidney transplants, and with the number of people with kidney disease climbing at a rate of approximately 5 percent per year, the reality of organ shortage is a mounting problem. According to the National Kidney Foundation (NKF), more than 26 million adults in the U.S. have chronic kidney disease (CKD). The Centers for Disease Control and Prevention correlates this to 1 in 10 Americans having some form of CKD, and statistics suggest that more than 350,000 Americans are on dialysis in a clinical setting.*
As with many diseases, there are stages to CKD, and treatment can help slow the progression of the disease. At the far end of the spectrum is end-stage renal disease (ESRD), also known as kidney failure. For a patient with end-stage renal disease, a kidney transplant is the only possible cure. More than 90,000 people in the U.S. are on the waiting list for a kidney transplant, and the number of kidneys available each year in the U.S. hovers around 18,000. In 2012, there were 16,812 kidney transplants in the U.S., according to the NFK.
When it comes to kidney transplants, there is a clear supply and demand issue.
For patients on the list, waiting becomes the name of the game, and dialysis is the key to waiting. Without dialysis, these patients will die. So they file in two or three times a week for multi-hour dialysis sessions, and they wait.
While they wait, researchers are racing to find, develop, and even grow alternatives.
Building and Bioengineering Solutions
Taken together, the growing number of patients, the limited supply of organs, and the high cost of kidney failure treatment create a staggering problem in the healthcare industry, and the race is on for new and improved technologies and approaches that may someday change the face of kidney disease.
The University of California San Francisco (UCSF) recently released reports of research on a new dialysis machine that may become a game-changer. The device they have developed is small—very small in comparison to clinical machines, machines that are often the size of a refrigerator. Not only does the device shrink the size requirement for dialysis filtering, but it is implantable. The device UCSF researchers have built, and which the Food and Drug Administration (FDA) has put on a fast-track for testing and approval, is, essentially, an artificial kidney and could dramatically change the reality of dialysis for patients in the future.
While an artificial kidney is one high-tech approach to improving the quality of life and treatment for patients with kidney disease, growing new kidneys for transplantation is another, and recent news from Massachusetts General Hospital in Boston, MA suggests lab-grown kidneys are not only possible but may be available sooner than you think.
In April, the New York Times reported that functional rat kidneys had been successfully bioengineered by scientists from Massachusetts General Hospital. Kidneys are complicated organs, and growing a kidney, from scratch, poses many challenges. Kidneys require more than one type of cell, for example. So the news from Massachusetts General is exciting.
Rather than attempting to grow new organs from ground zero, the lab-created kidneys in Boston involve decellularization, taking existing kidneys and separating them from their original cells. In this process, scientists create and use a "scaffolding," basically a skeleton of an organ's connective tissue from a patient that has been stripped of cells and onto which cells from another source or donor are encouraged to grow. The advantage of a decellularized kidney is that it contains a network of collagen, blood vessels, and other structural components necessary for sustaining kidney cell growth while maintaining the native shape and architecture of a normal kidney.
In the lab, cells derived from human umbilical cord tissue and newborn rat kidneys were then placed onto the scaffolding. After a few days, the cells regenerated new kidney tissue on top of the original kidney structure. After transplantation into rats, the kidneys successfully produced urine—a mark of a functioning kidney.
The scaffolding approach moves away from research involving using stem cells to grow complete kidneys and may have advantages when it comes to future implant success rates. In transplantation, the risk of rejection by the body is always an issue. With the scaffolding approach, researchers may be able to create organs that will be easier for the body to accept—they already look like kidneys because, in part, they came from kidneys and, potentially, from the patient's body. "By creating a skeleton or 'shell' of the organ to be produced and then re-populating this skeleton with kidney cells from another individual, it would not be necessary to use drugs that suppress the immune system," notes Leslie Spry, spokesperson for the National Kidney Foundation, in a recent article.
In concept, the scaffolding approach changes the direction for biomedical research on kidney creation. "If you put the organs side by side, it would be hard to tell which is the bioengineered organ and which is the real organ," said Dr. Joren Madsen, director of the Massachusetts General Transplant Center in a report published in The Boston Globe. According to the news story, Madsen plans to be part of the team that works on the next round of testing, possibly scaling the procedure up for use with bioengineered pig kidneys. Though the lab-grown kidney looks like a kidney, Madsen cautions that the functionality of the kidney still has a long way to go.
A Step Towards a Cure
The research on lab-grown kidneys is still in its beginning stages, and the availability of a such a kidney for humans may still be many years away. While the kidneys grown in these laboratory experiments do produce urine, they do not yet do all of the sophisticated tasks kidneys need to do. For example, the rat kidneys do not function as effectively as normal kidneys in reabsorbing nutrients from the blood. Based on the performance of the laboratory-grown rat kidneys, researchers have ideas for future experimentation using different types of cells, including stem cells.
Despite the challenges, the success of the bioengineered kidney has medical researchers and biotechnologists excited about the possibilities for growing kidneys to treat human disease.
Although researchers have been able to create functioning rat kidneys in the laboratory, the current process yields kidneys that are not as efficient as natural kidneys. There is still much room for improvement in terms of perfecting the art of bioengineering kidneys to ensure that patient-specific kidneys can be generated on demand and can perform at levels closer to natural kidneys. Understanding what proteins and factors are necessary for normal kidney growth may aid researchers in the race to improve the bioengineering of kidneys for use in future patient transplants.
Students who are interested in learning more about the power of stem cells in engineering organs can explore the molecular and biochemical factors that determine kidney synthesis in the following advanced hands-on science Project Idea:
- Creating a Kidney: How Stem Cells Might Be Used to Bioengineer a Vital Organ: what biological conditions would create the best environment for bioengineering a kidney? Utilize online bioinformatics databases to find out!
* A smaller number of patients use a form of home dialysis.