News - CMRB

18th November 2013

Scientists create, for the first time, “mini-kidneys" from human stem cells

Scientists create, for the first time, “mini-kidneys

A team of researchers from the Center of Regenerative Medicine in Barcelona (CMRB), the Salk Institute in California and the Hospital Clinic in Barcelona creates three-dimensional kidney structures in culture using human stem cells.

Up to now scientists have had a limited success in producing kidney cells in culture, therefore this new study is a scientific revolution.

This progress will facilitate the study of kidney diseases, the discovery of new drugs and is a step forward towards the implementation of stem cell-based therapies.

Kidney diseases constitute a serious public health problem. In the most serious cases they are incurable and patients require dialysis or a kidney transplant. Stem cells are a great tool for the study of many diseases and offer a great potential for the treatment of many of them. To that end, the researchers have to convert (differentiate) these stem cells into the cell type affected by the disease. However, until now scientists have had little success in converting stem cells into kidney cells. Now, the group led by the CMRB’s researcher and director, Juan Carlos Izpisúa Belmonte, has finally managed to create these kidney cells from human stem cells, and more importantly, they have shown that this cells are able to aggregate themselves in culture, forming three-dimensional kidney structures, virtually indistinguishable to the embryonic kidneys.

The scientific paper, now published in the prestigious journal Nature Cell Biology, represents a revolution in the field of biomedicine. The kidney tissues obtained by Izpisúa’s team will be a valuable tool, available to the scientific community, to investigate the development of the human kidney, the causes of kidney diseases and to test drugs in culture. "The generation of these well-organized 3D renal structures raises hope to think that one day we could use our own cells to regenerate our diseased organs, thus solving the shortage of organs for transplantation," explains Izpisúa.

Cutting-edge research

Recently, other research teams described the generation of brain and liver primordia from human stem cells. Thus, a Japanese group created functional liver buds and a research group in Vienna obtained micro-brains. To these two important achievements, Izpisúa’s team has now added these kidney primordia, and as in the previous two cases, the article has been published in a Nature group journal, of great prestige among the scientific community.

A new technology for the study of kidney diseases

To create these three-dimensional kidney structures, the researchers at Barcelona and California used embryonic stem cells and iPS cells obtained from human skin cells. The scientists developed a protocol by which they managed to convert stem cells in progenitor cells of the renal filtration and collection system in just 4 days in culture. These cells where then cultured with cells of the mouse metanephric blastema (a structure of the embryonic kidney). The result was that the two types of cells combined forming three-dimensional structures similar to the embryonic kidney, with a collection system exclusively made of human cells. Over time, these human progenitor cells recapitulated, in culture, the development processes of the human kidney. "Not only is it the first time that we have been able to create renal tissues in culture, but also that our studies have enabled the formation of three-dimensional structures typical of human organs," explains the first author of the paper, Ignacio Sancho-Martínez, "this will help us to study kidney development and the causes that lead to the onset of certain kidney diseases", says Núria Montserrat, co-author of the work.

In fact, Izpisúa’s group assessed the application of the methodology developed as a possible platform for the discovery of drugs and for renal disease modeling. To that end they created iPS stem cells from two patients diagnosed with polycystic kidney disease, a genetic disorder characterized by the formation of multiple fluid-filled cysts in the kidney that lead to decreased kidney function and kidney failure. With these cells, the researchers were also able to obtain kidney progenitor cells capable to aggregate with mouse cells to form kidney primordia, demonstrating the great utility of this technology for medicine. "One of the important clinical aspects of this research is that it makes it possible to reproduce human renal diseases in the laboratory and to test different therapeutic strategies in in vitro models", says Josep Maria Campistol, director of the Clinical Institute of Nephrology and Urology of the Hospital Clinic in Barcelona and staff member of the University of Barcelona and IDIBAPS, who also participated in this study.

A giant leap for regenerative medicine

The high incidence and poor prognosis of renal diseases are a major public health problem. The very little kidney self-repair capacity in humans highlights the urgent need for a better knowledge of kidney development and physiology. Up to know, the in vitro generation of kidney cells had demonstrated little success, being one of the major bottlenecks in kidney research. Additionally, the kidney has a very complex three-dimensional structure which involves many cell types. This groundbreaking study, which describes the creation of "mini" renal collecting systems, boosts the field of kidney regeneration and puts us one step closer to the goal of getting kidneys created from stem cells.

The CMRB: 6 years of research with induced stem cells

The Center of Regenerative Medicine in Barcelona (CMRB) is a research center sponsored by the Catalan Government’s Ministry of Health and the Carlos III Healthcare Institute. The CMRB’s mission is to study the molecular mechanisms underlying the regeneration of organs and tissues. Nowadays the group led by Juan Carlos Izpisúa Belmonte is a worldwide reference for the the generation of patient-specific iPS cells for in vitro modeling of genetic disorders.

The researchers on the study were: Yun Xia, Emmanuel Nivet, Ignacio Sancho-Martínez, Thomas Gallegos, Keiichiro Suzuki, Daiji Okamura, Min-Zu Wu, Ilir Dubova, Concepción Rodríguez Esteban, Núria Montserrat, Josep Maria Campistol and Juan Carlos Izpisúa Belmonte.

This research has been possible thanks to the Cellex Foundation. It was also supported by funds of La Marató de TV3 Foundation, CIBER-BBN and the Ministry of Economy and Competitiveness (TERCEL-ISCIII - MINECO).

For more information:

Directed differentiation of human pluripotent cells to ureteric bud kidney progenitor-like cells. Nature Cell Biology.

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