In the future, it may be possible to use healthy, lab-grown kidneys or renal spare parts to prevent and repair congenital renal defects. Satu Kuure, PhD, a researcher at the Institute of Biotechnology of the University of Helsinki, believes that scientists may soon be capable of recreating fully functional kidneys in vitro, in laboratory settings. Kuure is in charge of a research project studying the molecular mechanisms underlying kidney development as well as novel diagnostics and therapeutic tools for renal diseases. In September 2015, Kuure’s project received funding from the Academy of Finland within a new high-risk funding trial.
Kuure explains how the size of a person’s kidneys and the number of nephrons in each kidney are determined during foetal development. By studying and understanding mechanisms that regulate such processes, scientists could aim at developing methods with which kidney filtration capacity could be influenced. Larger kidneys would have more nephrons, which could help prolong kidney function.
“The two main processes we’re looking at are ureteric bud branching and nephron differentiation. The branching determines the future size and bean-like shape of the kidney. The ureteric bud branching during foetal life also determines the final number of nephrons in adult kidneys. Nephrons are the basic urine-filtering units of the kidney.”
Successful basic research in this area, Kuure says, could also contribute to the development of new, stem-cell-based forms of therapy.
“We need to gain more insights into kidney development. Additional research in this area could help us in further advancing in vitro organ culture and the prevention of renal damages. If we were able to maintain nephron progenitor cells in vitro and control their differentiation, we’d perhaps someday be able to develop additional nephron structures. Such structures could, for example, be transferred into poorly functioning kidneys to improve their filtration properties. I’m confident that engineering a fully functional kidney in a laboratory setting will soon no longer be science fiction. In vitro differentiation would be a way to mimic normal kidney development in the foetus,” comments Kuure.
Kidney damage is the third most expensive disease category in Finland
Satu Kuure is an experienced developmental biologist with 15 years of experience in kidney research. During this time, she has had the opportunity to follow the progress of research at first hand, but she still would like to see more research being devoted to discovering new, improved forms of therapy. In Finland, kidney diseases are the third most expensive disease category to treat, surpassed in cost only by cardiovascular diseases and cancer.
Kuure explains: “The currently available forms of treatment are fairly underdeveloped and ineffective. Take, for example, dialysis. Usually, even after three years of expensive dialysis treatment, patients will still need a kidney transplant.”
Congenital renal defects, such as renal failure or renal agenesis (missing one or both kidneys), are among the most common congenital defects together with anomalies of the heart and cleft lip and palate. New research knowledge can contribute to improving diagnostic accuracy in these cases.
“People with congenital renal defects are monitored throughout their lives. Our prospective discoveries could therefore also potentially have great impact in terms of the economy.”
Although a person can live a fairly normal life even with only one kidney, the risks for renal injury are greater in critical conditions. For example, in diseases such as cancer, intense medication may increase the risk for renal injuries for patients with only one kidney. “The damages occur when there aren’t enough nephrons in the body to filter out the waste. Extensive population-based studies have also shown that a reduced number of nephrons is associated with a higher incidence of high blood pressure,” says Kuure.
From risks to rewards
Controlled risk-taking is an essential element in the research projects funded under the Academy of Finland’s new high-risk funding scheme. Satu Kuure is well aware of the various risks contained in her own project. “There’s no guarantee that we’ll be able to turn our basic research findings into actual treatments,” she says.
At the day-to-day level, the risks concern the different genetic mouse models the researchers are working with. Using mouse models is an expensive and slow process. “The slowness is a risk from the perspective of producing publications. Unfortunately, there’s often a considerable time lag between the start of research and the publication of results.”
Kuure, however, tends to focus more on the rewards than on the risks. “Using genetically engineered mouse models is the only way forward if we truly want to understand a biological process such as development. This research method will allow us to work with the most realistic conditions available.”
Effective risk management, Kuure says, also relies on good collaborative networks and excellent work efficiency. It is important that each team member know what the other members are doing, so they can react accordingly.
Funding opens up new possibilities
Kuure is very pleased with the Academy of Finland’s funding.
“This new high-risk funding scheme is a great opportunity for any research team. It allows you to do things in completely new ways. It also gives hope to those who failed to secure funding earlier,” says Kuure.
The Academy of Finland launched the new scheme as a funding trial to support particularly innovative and high-quality projects confirmed to involve promising risk-taking in terms of research. Granted by the Academy’s Research Council for Health, the funding is aimed at encouraging bold approaches to research that are needed if scientific breakthroughs and the renewal of scientific activity are to succeed. The total funding amounted to around 1.7 million euros granted to ten projects in the health research field for a period of 16 months. After the 16-month funding period, the Research Council for Health will decide on possible follow-on funding for the projects.
Finnish text: Anna-Riikka Oravakangas
Photo: Anita Westerback
- Academy of Finland supports scientific risk-taking with purpose-made funding (Academy press release, 2 Sep 2015)