Researchers are a step closer to learning how congenital kidney defects develop in the fetus and how they might be prevented, a new report shows.
For the first time, they can watch miniature human fetal kidneys develop in test tubes over periods that simulate the course of a pregnancy.
So-called kidney organoids have been grown in test tubes before, but only starting with pluripotent stem cells – immature cells found in early embryos that can differentiate into any cell type in the body but without the tissue-specific characteristics that would allow them to perform an organ’s specialized functions.
In contrast, the new organoids are grown in test tubes using the same fetal progenitor stem cells that are destined to develop into human kidneys. These cells are capable of building, maintaining and repairing specific organs – in this case, the kidneys.
While kidney organoids grown from pluripotent stem cells have survived in test tubes for weeks, the new organoids built from the human fetal kidney stem cells can survive and grow for six to eight months, essentially allowing researchers to observe human kidney development as it would happen during a pregnancy, the research team reported in The EMBO Journal.
“Once we had the tissue stem cells coming from the developing human kidney in the Petri dish, they did the job because this is what they do in nature,” said Dr. Benjamin Dekel of Safra Children’s Hospital at Sheba Medical Center and Tel Aviv University, who led the research.
“The cells are self-assembling. They know how to self-organize and how to self-renew, (that is) make copies of themselves,” Dekel said.
At the same time, Dekel continued, the cells begin to differentiate, developing qualities that make them appropriate for different roles. Researchers can watch as kidney tubules, ducts, blood vessels and other renal tissues are formed.
In his clinical practice, Dekel treats children with kidney diseases.
He hopes eventually to use the organoids to study kidney malformations and to isolate genes that lead to birth defects, develop new treatments in the field of regenerative medicine and test the toxicity of drugs during pregnancy on fetal kidneys.
In the meantime, he said, it’s frustrating to watch as his patients’ chronic kidney disease worsens into end-stage renal disease.
“Then we need to give them a kidney transplant or to put them on dialysis, which is really a very poor solution,” he said.