FLICKR, TAREQ SALAHUDDINCan organs like kidneys be made, to save lives? How efficiently can we custom-make highly differentiated cells, like podocytes (the kidney’s filtering cells), in Petri dishes and use them to develop better future therapies?
At a TED conference held in Long Beach, California, in 2011, Anthony Atala of Wake Forest University’s Institute for Regenerative Medicine demonstrated printing something that looked a lot like a human kidney by using live cells deposited in layers. Although Atala’s 3-D printed kidney may not have possessed the filtering capabilities necessary to function in the human body, it might be just a matter of time before this medical innovation becomes a reality, helping people in dire need of a transplant. Indeed,10 years ago, one of Atala's young patients, Luke Massella, received an engineered bladder made using similar technology.
Printing a human kidney, albeit non-functional, takes us a step closer to utilizing the enormous potential of stem cells from different sources. In a 2007 Nature Biotechnology paper, Atala’s group demonstrated that amniotic fluid can serve as a source of stem cells with enormous potential for therapeutic purposes. In a 2012 article in the Journal of Biomedicine and Biotechnology, Shinya Yokote, Shuichiro Yamanaka, and Takashi Yokoo from the Jikei University School of Medicine in Japan emphasized the potential of stem cell-based therapies for injured tissue repair in chronic kidney diseases and de novo whole-kidney regeneration.
Practicing regenerative medicine and building a whole tissue or organ from stem cells will definitely be a huge step toward solving the problems of organ donor scarcity and organ rejection. The first cadaveric kidney transplantation was performed on June 17, 1950, on a woman named Ruth Tucker in Illinois. The experimental procedure extended her life by only five years because immunosuppressive therapy was not administered at the time of transplantation. This was followed by one of the first kidney transplants from a living patient—in Boston in 1954—between identical twins, which gifted eight more years of life to the recipient. Joseph Murray, who was one of the physicians to perform the transplant, received a Nobel Prize in 1990 for this and related work. Since then, researchers have come a long way, mainly by largely overcoming the major barrier of organ rejection through the development of better immunosuppressive therapies. But organ replacement remains a very critical issue because of side effects related to immunosuppression and a dearth of donors.
Many disorders can contribute to end-stage renal disease, which is the main indicator for kidney transplantation. Diabetes alone, which is on the rise the world over, is the major cause, responsible for more than 40 percent of all end-stage renal disease cases in need of kidney transplant. More than 20,000 patients receive kidney transplants per year in the U.S. at a cost of around $262,900 each, including pre- and post-transplant care. That sounds like lot of money, but surprisingly, it is the cheapest organ to transplant compared with others, such as heart, lung, liver, pancreas and intestine. The United Network for Organ Sharing database states that the number of people waiting for kidney transplants in the U.S.—as of September 6, 2013—is 104,529, 80 percent of whom are already on dialysis. This waitlist will continue to grow and wait times will increase to 10 years unless there is a significant increase in the number of kidney transplants performed each year.
On the other end of the spectrum, there is a critical need to better understand the pathogenesis of diseases that lead to end-stage renal disease and to establish models for simple and cost-effective in vitro screening of new treatments. Research on differentiated kidney cells, particularly podocytes that can be cultured in the lab, may hold some answers. Although there are a few human- and mouse-derived cell lines that potentially differentiate into functional podocytes, there is a need for better cell lines and systems that mimic the in vivo situation more closely. Sharon Ricardo’s group at Australia’s Monash University recently reported in PLOS ONE on the generation of differentiated podocytes from human induced pluripotent stem cells. These cells have a high proliferative ability and broad differentiation capacity, which may offer a major advance for both research and clinical applications. A further challenge is to study these podocytes in the context of their neighboring cell types and also to develop three-dimensional cultures that mimic the in vivo situation more closely.
Shipra Agrawal is a research scientist at Nationwide Children’s Hospital in Columbus, Ohio.