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Opinion: I Want My Kidney

With the advent of xenotransplantation, tissues made from cell-seeded scaffolds, and 3-D-printing, custom-made organs must be right around the corner.

By | November 7, 2013

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.

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Comments

Avatar of: ProfessorK

ProfessorK

Posts: 11

November 14, 2013

I find it stirring and a little disappointing that we are still talking about stem cell capability from amniotic fluid. It seems like someone would challenge the status quo and open up the idea of options outside our current understanding of stem cells. Where are they?

Avatar of: Duncalicious

Duncalicious

Posts: 4

November 14, 2013

I realize this is an opinion piece, but at first glance it sounded like it might talk a little bit more about the promise of the future. What of this so-called "organ regeneration era"?

Avatar of: RJohnson

RJohnson

Posts: 9

November 15, 2013

The organ regeneration era? Sounds like an exciting one. But as you asked, what of it. I don't pretend to know that there is much happening with it right now. At least those aren't being created by printers.

But that again, that's not regeneration. Which if was possible, I'd be ecstatic.

Avatar of: HChapman

HChapman

Posts: 9

November 29, 2013

I suggest you guys take a look at this article as well:

http://www.businessinsider.com/how-regeneration-works-2013-7

Considering the many avenues currently being pursued by researcher to reach the same goal, it wouldnt be surprising to see the main-stream practice down the road being a combination of all of these approaches. Maybe a 3D printed organ valve utlizing the seed scaffolding for support and then using the body's own regenerative process to seemlessly adopt the transplanted valve and heal/regenerate the rest of the damaged organ. 

Another article by the same author talks about a rising 'regeneration era' as well, Duncalicous. Hope this was helpful.

Avatar of: BW012375

BW012375

Posts: 6

November 29, 2013

I certainly agree that the correct motivator of stem cell research should lie in finding ways the body can regenerate. Were the article a little more reflective of the true science behind, as the Kidney piece is, it would be an excellent article.

Avatar of: HChapman

HChapman

Posts: 9

November 29, 2013

I couldn't agree more. The author's conviction is certainly there, and the idea of organ regeneration is a fruitful one. Tie those two together, and we've got the beginnings of something.

A lot to be said for having multiple avenues for this, as well as the fact people are beginning to understand that organ regeneration is THE goal for stem cell research.

Avatar of: NRA

NRA

Posts: 5

November 29, 2013

Regardless, we need less background on WHY it's useful. More on HOW it is, along with WHAT it is.

One thing I did take away from the Business Insider article is a hope that somewhere, someone is actually putting the patients best efforts in mind. I realize that might be a long stretch, and in saying so I sound jaded, but what have healthcare or scientific research done for us lately?

Avatar of: CBerrien

CBerrien

Posts: 8

November 29, 2013

I've come across some other articles by Xu. I like how his columns aren't afraid to call out the status quo. 

Avatar of: THenry02

THenry02

Posts: 12

November 29, 2013

Big fan of Anthony Atala's work. I'm always interested in hearing more about his thoughts on the industry. The potential for regeneration is growing, which makes this a very exciting time.

Curious article on organ regeneration by the way.

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