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WHO International Clinical Trials Registry Platform

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Stem cells from pee?

A way to generate stem cells has been found using pee! Stem cells isolated from human urine appear to be more stable than skin stem cells, and cells from urine can also generate countless other cell lines. Urine collection is a non-invasive way to get stem cells from Down syndrome and other vulnerable patient populations, and may become a new and sound way to study human disease.


One of the biggest challenges in studying Down syndrome is finding the right research model. Animal cell lines are limited in how they can mimic human diseases and experimental results don't always apply to human patients. Pee stem cells hold the same research potential as classical stem cells, but are less invasive to collect from children or patients with intellectual disability.


Researchers from Case Western Reserve University School of Medicine have developed a breakthrough technique to harvest cells directly from urine.


The non-invasive technique, described in the journal Stem Cells Translational Medicine, creates urgently needed research models for Down syndrome and for other neurologic conditions.


"For the first time, we were able to create induced pluripotent stem cells — iPSCs — of persons with Down syndrome from urine samples. A significant improvement in iPSC technology. And, an important step toward development of human cell-based platforms for testing new medications designed to improve the quality of life of people with Downs."

Alberto Costa MD PhD, Professor, Division of Pediatric Neurology, Department of Pediatrics, Department of Psychiatry, Case Western Reserve University, Cleveland, Ohio, USA, and study leader.


Costa's technique overcomes ethical challenges related to harvesting stem cells previously collected via skin biopsies. The new technique allows researchers to build collections of stem cells for use in future work.

Stem cells generated from urine also appear to be more stable than stem cells from skin biopsies, as skin cells are exposed to sunlight and often have DNA damaged via ultraviolet radiation. Stem cells generated by Costa's team were manipulated using laboratory techniques designed to limit DNA damage.


The resultant iPSCs can be reliably grown into cell types including neurons and heart cells. This study is the first to generate such cells from urine cultures.


The team generated iPSCs from 10 individuals with Down syndrome, which can be used in other research modeling Down syndrome disease states.

Abstract
Down syndrome (DS) is a genetic disorder caused by trisomy 21 (T21). Over the past two decades, the use of mouse models has led to significant advances in the understanding of mechanisms underlying various phenotypic features and comorbidities secondary to T21 and even informed the design of clinical trials aimed at enhancing the cognitive abilities of persons with DS. In spite of its success, this approach has been plagued by all the typical limitations of rodent modeling of human disorders and diseases. Recently, several laboratories have succeeded in producing T21 human induced pluripotent stem cells (T21-iPSCs) from individuals with DS, which is emerging as a promising complementary tool for the study of DS. Here, we describe the method by which we generated 10 T21-iPSC lines from epithelial cells in urine samples, presumably from kidney epithelial origin, using nonintegrating episomal vectors. We also show that these iPSCs maintain chromosomal stability for well over 20 passages and are more sensitive to proteotoxic stress than euploid iPSCs. Furthermore, these iPSC lines can be differentiated into glutamatergic neurons and cardiomyocytes. By culturing urine-derived cells and maximizing the efficiency of episomal vector transfection, we have been able to generate iPSCs noninvasively and effectively from participants with DS in an ongoing clinical trial, and thus address most shortcomings of previously generated T21-iPSC lines. These techniques should extend the application of iPSCs in modeling DS and other neurodevelopmental and neurodegenerative disorders, and may lead to future human cell-based platforms for high-throughput drug screening. Stem Cells Translational Medicine 2017.

Significance Statement
In this study, we describe a method for derivation, differentiation, and characterization of trisomy 21 (T21) induced pluripotent stem cell (iPSC) lines from urine-derived epithelial cells using nonintegrating episomal vectors. We show that these iPSCs maintain chromosomal stability for 20 passages, can be differentiated into glutamatergic neurons and cardiomyocytes, and are more sensitive to proteotoxic stress than euploid iPSCs. We have been able to generate iPSCs noninvasively and effectively from participants with Down syndrome (DS) in an ongoing clinical trial, and thus address most shortcomings of previously generated T21 iPSC lines. These techniques should improve the quality and extend the application of iPSCs in modeling DS and may lead to future human cell-based platforms for high-throughput drug screening in translational preclinical studies, and should help streamline cell-banking applications.

Funding for the study was provided by grants from ALANA USA Foundation (Contracts 124124 and 200381), the Alana CWRU/MIT Collaborative Fund, a grant from the Ohio Department of Developmental Disabilities, and charitable contributions from the Awakening Angels Foundation. Bruna Zampieri, PhD was supported by a Postdoctoral Fellowship from the Conselho Nacional de Desenvolvimento Científico e Tecnológico, Brazil (CNPq/MCTI, 202237/2014-1).
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Apr 7, 2017   Fetal Timeline   Maternal Timeline   News   News Archive   



Stem cells generated from urine appear to be more stable than those from skin biopsies
Image Credit: KOHLER

 


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