Gloved hand holding slide in front of microscope

Case Western Reserve University researchers develop breakthrough technique to advance Down syndrome research

Researchers from Case Western Reserve University School of Medicine have developed a breakthrough, noninvasive technique to develop stem cells strongly relevant to the study of Down syndrome.

Writing in the journal STEM CELLS Translational Medicine, the researchers detail their development of an approach using human cells that address shortcomings of earlier efforts involving human cells—as well as those of animal models.

“For the first time, we were able to create induced pluripotent stem cells, or iPSCs, of persons with Down syndrome by cells obtained from urine samples,” said Alberto Costa, study lead and professor of pediatrics and psychiatry at Case Western Reserve University School of Medicine. “Our methods represent a significant improvement in iPSC technology, and should be an important step toward the development of human cell-based platforms that can be used to test new medications designed to improve the quality of life of people with Down syndrome.”

One of the biggest challenges in studying Down syndrome is finding the right research model. Animals and established cell lines are limited in their ability to mimic human disease, and results don’t always translate to patient populations. Stem cells hold enormous potential as research tools that can be collected directly from patients and grown into innumerable cell types. But harvesting stem cells can be invasive—a challenge the Case Western Reserve team addressed by using cells from patients’ urine. In addition, their technique employed methods designed to limit DNA damage. The resultant iPSCs can be reliably grown into many cell types relevant for Down syndrome research, including neurons and heart cells. The study is the first to successfully generate such cells from urine cultures.

Not only does the research provide a path toward urgently needed research models for Down syndrome, but it also shows promise for modeling other neurologic conditions.

Costa’s technique also overcomes ethical challenges related to harvesting stem cells that have previously been collected via skin biopsies. As he and his authors noted in their paper, taking skin biopsies from individuals with Down syndrome sometimes is questioned by institutional research boards or ethics committees, and some parents also decline the procedure as well. This new technique allows researchers to more easily build collections of stem cells for use in future studies.

Stem cells generated from urine also appear to be more stable than those generated via skin biopsies. Since skin cells are exposed to sunlight, they often have DNA damage caused by ultraviolet radiation. The stem cells generated by Costa’s team did not involve cells exposed to the sun.

In total, Costa’s team generated iPSCs from urine donated by 10 individuals with Down syndrome that can be used by his team and other researchers interested in modeling Down syndrome disease states. The new technique can also be used to generate additional cell lines from Down syndrome patients or other vulnerable populations.