Modeling kidney diseases using kidney organoids derived from embryonic and adult stem cells
Birth defects are the most common cause of kidney failure in children. Modeling the congenital renal defect using stem cells and investigating the ways of its formation can lead to a significant improvement in renal function, and in the patient's quality of life.
Prof. Benny Dekal, Director of the Pediatric Nephrology Department and the Pediatric Stem Cell Research Institute, at the Safra Children's Hospital in Tel Hashomer, and the Vice-Dean of the Faculty of Medicine at Tel Aviv University, and Dr. Dorit Omer, a senior researcher at the Pediatric Stem Cell Research Institute, are developing, with the assistance of a research grant From the National Science Foundation, methods for growing 3D kidney tissue in culture outside the body. "Using these tissues," say the researchers, "we are investigating ways to accurately model diseases outside the body. The models make it possible to study the mechanisms of hereditary kidney diseases and to find new and even personalized medicines."
What is the question?
How is it possible to model kidney diseases of a particular patient?
It is possible to grow kidney cells from a variety of sources - to sort kidney cells from embryonic stem cells, to extract and culture mature cells from the kidney, or alternatively to collect or grow kidney cells from the patient's urine. Each cell source is suitable for a certain modeling of diseases. For the purpose of clinical research, it is necessary to create organoids from these cells, which are 67D models of tissues (grown outside the body), which simulate the structure and function of the organs in the body. ecad-ki2-dapi-XNUMX
The use of organoids as a tool for modeling kidney diseases is based on a thorough understanding of the types of stem cells and their suitability for the specific type of disease. The first type is embryonic stem cells, which are characterized by a high potential to differentiate into different cell types. In kidney research, they are used to create organoids that simulate kidneys in the embryonic stage, and are particularly suitable for the study of diseases that develop during the embryonic period, such as congenital malformations of the urinary tract and kidneys.
Another source is induced stem cells, which are produced from adult cells that have undergone a genetic "rejuvenation" process to a stage very close to that of embryonic stem cells. These cells allow researchers to create organoids that simulate kidneys at different stages of kidney development. From such cells it is possible to create cell lines of the patients themselves which carry the specific mutation.
A third source is first embryonic kidney cells, which are taken directly from aborted embryos and simulate the embryonic kidney in a three-dimensional tumor form over time in the most reliable way. They are a control set for kidney cells sorted from embryonic stem cells.
Another source is mature cells from the kidney and urine. The use of these cells is intended to create organoids that simulate adult kidneys, and enables the study of kidney diseases that develop after birth and especially during adult life. This is an important approach to developing targeted and personalized treatments.
The use of organoids as a tool for modeling kidney diseases is based on a thorough understanding of the types of stem cells and their suitability for the specific type of disease.
For example, in one case, a girl suffering from cystic kidney disease caused by a genetic mutation was admitted to the intensive care unit. In this disease, cysts develop in the kidneys and grow over time, replacing the healthy tissue, causing the kidneys to enlarge significantly and impairing their function. The considerable growth of the kidneys caused pressure on the chest and breathing difficulties. The team used the girl's urine samples to collect kidney cells that carry the genetic mutation and build a 3D kidney organoid for the patient. The organoid simulated her illness and allowed the team to test a series of drugs on it. Finally, they identified a novel combination of two drugs in clinical use that could reduce the size of the cysts.
"It is important to combine basic research with clinical application, for the benefit of the patients," the researchers explain. "The organoids extracted from the urine are evidence of this. Sometimes, those who dictate the research direction are patients who arrive in a difficult condition and are required to find innovative drugs for their kidney disease."
Life itself:
Prof. Benny Dekal, 57, father of three, a 26-year-old daughter, and 21-year-old twins. In the medical cap, he heads the pediatric nephrology department at the Safra Children's Hospital at the Sheba Medical Center in Tel Hashomer. In the research hat, he is the director of the Institute for Stem Cell Research in Children and the Sagol Center for Regenerative Medicine. In the academic hat, he is in charge of the Ezekiel and Pearl Kleiman Chair of Nephro-Urology, and Vice Dean for Research and Innovation at the Faculty of Medicine at Tel Aviv University. He believes that solving scientific medical problems requires passion and perseverance. Swims in the sea in summer and winter. Dorit Omar
Dr. Dorit Omer, married and mother of three (7, 11, 13). Senior researcher in Prof. Dekel's laboratory at the Sheba Medical Center, where she also did her doctoral thesis on the growth of induced kidney cells from different sources. She later carried out post-doctoral research at the Hebrew University of Jerusalem, in collaboration with Prof. Eran Meshorer in developing methods for growing kidney tissue from stem cells.
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