Bioprinting a Kidney: Hope or Hype

Organ shortage remains as a global crisis with no sight of a decrease in demand. In the US alone, the current number of people on a waitlist for organ transplantation stands at over 120,000 and >83% are awaiting for kidney transplants [1]. Of those requiring transplants, only ~17% receive a kidney transplant, ~5% will die and the remaining 78% are still on the waitlist.

Kidney transplants is not the end-all be-all

Even if you were the lucky 13%, having a new transplant means you have to be on immunosuppresive drugs for the rest of their lives to minimize organ rejection and continue to be vigilant with their health.

The other option

For those who are less fortunate, which is the majority, they have to be on dialysis. This means you will have to go to a treatment center for hemodialysis every 2-3 days to get your blood filtered. For those who choose home-based treatment, either hemodialysis or peritoneal dialysis, this will have to be done everyday. Dialysis treatment affects the quality of life, it is expensive and the average survival rate is around 3-5 years [2] though numbers seem better for those on peritoneal dialysis and in younger patients.

Due to these limited options, demand for a healthy kidney is high and people in desperation are willing to pay, leading to the surge of unethical kidney harvesting in the black market.

Tissue engineering and bioprinting

With this looming crisis on the horizon, researchers around the world are actively finding solutions through tissue engineering and bioprinting approaches. However, this is not a simple approach, re-creating a fully functional organ requires not only a deep understanding of the biology, its architecture and the tissue microenvironment but also requires the tools and resources to create them ex vivo. Thus we may still be years or decades away from a fully functional bioprinted kidney.

One of the major hurdles that have limited progress during the early years of this field was the lack of functional human renal cells. Fortunately, the tide began to change in 2012 when researchers figured out how to differentiate induced pluripotent stem cells (iPSCs) into renal cells and subsequently kidney organoids [3]. These breakthroughs accelerated progress in the development of tissue models [4] and organoids [5] for drug screening, toxicity testing and regenerative medicine. 

Notable research
One notable work comes from a group of Harvard researchers from the Wyss Institute led by Dr. Jennifer Lewis who recreated the convoluted renal proximal tubules, a region that suffers the most damage during renal injury [4]. Traditional 2D cultures of proximal tubule cells cannot recapitulate in vivo nephrotoxicity as they lose both phenotypic and functional aspects that are important. Using bioprinting tools, Lewis and her team was able to program and fabricate advanced human kidney tissue models that were superior to 2D controls on demand. The proposed model has been validated in vitro with a nephrotoxin, showing a dose-dependent response.

Noticeable progress was made from a group of researchers in Australia led by Melissa Little at Murdoch Children's Research Institute and an industry partner - Organovo [5]. Using the NovoGen MMX 3D bioprinter developed by the company, the team was able to generate highly reproducible kidney organoids from human iPSCs for high-throughput drug screening applications.  

Another key and recent progress made by researchers at the Wake Forest Institute for Regenerative Medicine led by Sang Jin Lee was the discovery and development of a photo-crosslinkable kidney ECM-derived bioink [6] which supported the survival and maturation of bioprinted human kidney cells. These early results show great promise to its potential use for creating complex bioprinted renal constructs that can mimic the native tissue. 

Looking ahead
In order to continue making progress, we must bring together the best minds and nurture the next generation from multiple disciplines to solve this complex challenge. Bioprinting a kidney will require the expertise and experience from a vast area covering the healthcare, medical, bioengineering, mechanical engineering, material science, chemistry and beyond. We should not let our imaginations be limited to what we know and continuously push ourselves to gain new knowledge or skills needed as technology advances.

To learn more about bioprinting technology, check out this beginner course in bioprinting. 


References:
[1] Organ donation and transplantation statistics. Online resource from National Kidney Foundation
[2] Kidney dialysis life expectancy from http://www.buzzle.com
[3] Chuah and Zink. Stem cell-derived kidney cells and organoids: Recent breakthroughs and emerging applications. Biotechnology Advances (2017). vol 35 p150-167.
[4] Homan et.al. Bioprinting of 3D convoluted renal proximal tubules on perfusable chips. Scientific Reports (2016) vol.6 - 34845.
[5] Higgins et.al. Bioprinted pluripotent stem cell-derived kidney organoids provide opportunities for high content screening. bioRxiv (2018). 
[6] Ali et.al. A photo-crosslinkable kidney ECM-derived bioink accelerates renal tissue formation. Advanced Healthcare Materials (2019). vol.8 (7)

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