In this interview, Professor Hermann Haller, M.D., faculty member at the MDI Biological Laboratory (Bar Harbor, ME, USA) and director of the Department of Nephrology and Hypertension at Hannover Medical School (Germany), discusses the possibility of utilizing stem cells for engineering new renal tissue and kidneys.
Chronic renal failure is a major and growing medical problem throughout the world. Dialysis and kidney transplantation can serve as successful strategies to treat patients who have lost kidney function; however, regenerative medicine could make it possible to replace lost or damaged tissue, or replace the kidney entirely.
In this interview, Professor Hermann Haller, faculty member at the MDI Biological Laboratory (Bar Harbor, ME, USA) and director of the Department of Nephrology and Hypertension at Hannover Medical School (Hanover, Germany), discusses his career to date and the possibility of utilizing stem cells to generate new kidneys, including using animal models to understand the pathways involved, 3D bioprinting and the timeline to the clinic.
Professor Hermann Haller, M.D.
Professor Hermann Haller, M.D., is an internationally acclaimed expert in the areas of kidney disease, hypertension and renal transplantation. He has made important contributions to the fields of diabetic nephropathy, pregnancy-associated disease, renal vascular hypertension and transplantation. Professor Haller has been the Director of the Department of Nephrology and Hypertension at Hannover Medical School since 1999, where he has established an internationally renowned clinic for renal disease and hypertension. He has received numerous prizes for his scientific achievements, and has been president of the German Hypertension Society and board member of the European Society of Hypertension. He is also co-editor of several books, and associate editor of national and international journals.
Could you please kick off the interview by telling us what your current work at the MDI Biological Laboratory and Hannover Medical School entails?
I’m a clinician—scientist, so on the one hand I’m dealing with patients. For example, in Hanover I established the new Interdisciplinary Transplant Center for Clinical Research, the most experienced center for kidney transplantation in Germany. Highlights of the program are both acute treatment and long-term follow-up care. On the other hand, I’m a scientist who is trying to understand how the kidney heals and how we can make the kidney work again, and particularly whether we can replace kidney function by making new kidneys.
How do you anticipate that identifying the molecular mechanisms underlying the regenerative ability of animals such as the skate could help alter the way renal failure is treated?
Here at the MDI Biological Laboratory, we identified the regenerative capacity of the shark and skate almost 15 years ago. These animals can make new renal tissues when their kidneys are damaged. Since their tissue looks like ours, we are trying to understand why they can do that and we cannot. The mechanisms we have learned from fish are helping us conduct experiments with stem cells in order to generate renal tissue and eventually new kidneys, like the fish.
“The mechanisms we have learned from the fish are helping us conduct experiments with stem cells in order to generate renal tissue and eventually new kidneys.”
What are the steps to finding out if stem cells can be manipulated to create new kidneys in humans?
We’ve learned a lot over the last couple of years about how to manipulate stem cells in order to make renal tissue. Groups in Australia and the United States have shown that we can make almost all of the cells we need to make a new kidney. Recent publications (see ‘Further reading’ below) have done a wonderful job in demonstrating that a lot of stem cell technology can be used to make the different parts of the human kidney. The main challenge now is to bring these elements together to make a 3D artificial kidney from cells.
“A reasonable time frame [for replacing dialysis and transplantation with new kidneys] would be 5—10 years to generate a new kidney, then realistically not more than 20 years to put it in humans.”
What do you think a realistic timeline for replacing dialysis and transplantation with new kidneys is?
This is always a very difficult question to answer! Science moves ahead in leaps. We have to work continuously, but it is very difficult to anticipate what is going to happen. Think of the original airplanes and the ones we have today: we only found out how we can fly 100 years ago, and then there was rapid development. The same is true for the tissue replacement that we are working on at the moment. I cannot tell you exactly, but a reasonable time frame would be 5—10 years to generate a new kidney, then realistically not more than 20 years to put it in humans.
What are the biggest challenges in this area of research and how could they be overcome?
The main hurdles that we have already overcome have been how to manipulate stem cells to make renal tissue and how to use and induce cells from individual patients into stem cells; this was the most important and basic step. Now we have to make 3D models of the kidney and learn from fish and other animal models how to put all these cell types together. Creating 3D modeling of renal tissue and then putting it in patients and hooking it up to the circulatory and urinary systems will be the main hurdles.
“I can anticipate that, with the stem cell technology, we will have factories producing new organs.”
What impact do you hope engineering a whole kidney would have on patients’ health, the healthcare system and the economy?
In kidney disease we are in a fortunate position in that we can already replace kidney function with dialysis and donor transplantation, so we already know it works. The stem cell-based artificial kidneys we are working on will have no issue with immunology, so will be better for transplantation than donor transplants, and they will have fewer chronic problems than dialysis. So we can treat patients with chronic diseases by replacing their kidney function and have a huge impact on the longevity of these patients. I can anticipate that, with stem cell technology, we will have factories producing new organs.
“All these groups from different areas — not only medical doctors, but engineers and other technologies — need to come together to make new kidneys, exactly like in the Apollo program. Only when we work together we will be able to create a new kidney.”
You’ve compared the work involved in regenerating a kidney to the work on the Apollo moon landing. Could you please elaborate on this statement?
The Apollo moon landing and regenerating a kidney are very comparable — you need a goal, which is the most important thing, then you need different groups working together under the umbrella of this one goal because it is not only one lab demonstrating that it can induce pluripotent stem cells into renal tissue. You need other labs’ experience in the vasculature, the urinary tract, using laser technology to make the models and using engineering to encapsulate the cells. Then you need to know how to be able to hook the tissue up in patients. All these groups from different areas — not only medical doctors, but engineers and experts in other technologies — need to come together to make new kidneys, exactly like in the Apollo program. Only when we work together we will be able to create a new kidney.
What technologies do you see being used to achieve whole organ kidney generation? For example, a group has recently used 3D bioprinting to develop a proximal tubule-like structure. Is this a technology that you can foresee being used?
I think that laser technology and cell printing are important. I can envision large-scale cell printing on the one hand, or making 3D structures from materials that will dissolve once the renal tissue is formed. I don’t know at the moment how the technology will work in the end. We are trying different avenues and we will see in the future which one will be most successful or whether we will have different approaches. However, laser technology and new materials, especially the sugar-coated materials that we are using at the moment, and the biology of the stem cells – how to really differentiate them finally into a polished version of a new kidney – will be important.
“I think it’s very important to make people understand what is actually going on in the labs of both clinicians and scientists.”
Recently you delivered a MDI Science CafÃ© presentation entitled ‘From Fish and Mice to Men: How to Make a New Kidney’. What else do you do to promote public engagement with science?
I think it’s very important to educate the public about how we can use modern technology and science to improve the health and quality of life of our patients, and also to make them understand what we as scientists are actually doing. I do interviews and I give lectures at scientific meetings and also to the public. I also try to use electronic media like blogs where I can write more personally about what the problems are and how we can meet the challenges of developing a new kidney. I think it’s very important to make people understand what is actually going on in the labs of both clinicians and scientists.
What other whole organ engineering breakthroughs do you see occurring in the next 10 years?
In terms of tissue regeneration and replacement, we are urgently awaiting neural tissue — peripheral nerves — and replacement of disabled heart tissue. I think we are already doing quite a bit with liver regeneration — the liver is one of the easier targets for regeneration — and then it is bone and cartilage. We are already using engineered cartilage in patients and we are in the clinic with bone too. We are not there with the kidney, heart and neurology, but I think these are the breakthroughs that are most important.
Another area is wound healing: wound healing is a major medical problem and replacement with regenerated tissue soft tissue would be a major breakthrough.
“We are already using engineered cartilage in patients and we are in the clinic with bone too. We are not there with the kidney, heart and neurology, but I think these are the breakthroughs that are most important.”
What further investigations do you have planned?
In addition to studying the mechanisms in fish and other animal models and making new models, we will use laser-based technologies to better understand differentiation of the various cell types. I’ve already talked about the induction of cell differentiation from stem cells. The challenge is now to understand how these cells interact with each other.
In the human kidney you have tubular structures next to vascular structures next to interstitial tissue, and this is what we have to understand — how the different departments communicate. At the MDI Biological Laboratory, we are setting up new laser-based technology that allows us to have these different compartments next to each other under natural conditions and to study the communication of the different cells with each other in order to help us understand how the kidney functions and how the cells function so that we can manipulate them to make renal tissue.
“In the human kidney you have tubular structures next to vascular structures next to interstitial tissue, and this is what we have to understand — how the different departments communicate.”
Do you have any final thoughts or comments that you’d like to add?
One of the most important issues is the education of young people in science. We need to get young people interested in the research we are doing. We have to educate them and spark their curiosity in these projects. One of the things we are doing at the MDI Biological Laboratory is building a training lab and bringing in international mentors to get young people interested in the laboratory’s scientific goals. I think education is the most important goal of them all.
Learn more about the research being conducted at the MDI Biological laboratory with this podcast featuring Dr Sandra Regier (MDI Biological Laboratory; Bar Harbor, ME, USA) – listen now.
- Nothing to declare
- Elger M, Hentschel H, Litteral J, Wellner M, Kirsch T, Luft FC, Haller H. Nephrogenesis is induced by partial nephrectomy in the elasmobranch Leucoraja erinacea. J Am Soc Nephrol. 14(6):1506-18 (2003)
- Little MH, Combes AN, Takasato M.Understanding kidney morphogenesis to guide renal tissue regeneration. Nat Rev Nephrol. 12(10):62 (2016)
- Rabelink TJ, Little MH. Stromal cells in tissue homeostasis: balancing regeneration and fibrosis. Nat Rev Nephrol. 9(12):747-53 (2013)
- Little MH, Kairath P. Regenerative medicine in kidney disease. Kidney Int. 90(2):289-99 (2016)
- Morizane R, Lam AQ, Freedman BS, Kishi S, Valerius MT, Bonventre JV. Nephron organoids derived from human pluripotent stem cells model kidney development and injury. Nat Biotechnol. 33(11):1193-200 (2015)
- Lam AQ, Bonventre JV. Regenerating the nephron with human pluripotent stem cells. Curr Opin Organ Transplant. 20(2):187-92 (2015)