In 2010, a collaborative project between researchers from the Salk Institute for Biological Studies, the University of California, San Diego, and Penn State University, investigated whether induced pluripotent stem cells (iPSCs) could be utilized to study complex neurodevelopmental disorders, like autism spectrum disorder (ASD), to develop better targeted therapies[1]. By employing cell lines obtained from Coriell, the team successfully transformed skin cells, or fibroblasts, from patients with Rett syndrome (RTT), a genetic disorder that formerly fell within the autism spectrum, into iPSCs. From these iPSCs, the researchers were able to generate neurons to better understand their structure and function in individuals with RTT, and more broadly, ASD.
Rett syndrome is a neurodevelopmental disorder that affects almost exclusively girls and is characterized by a slowing of development, seizures, and intellectual disability. It affects one in every 10,000 to 15,000 female births worldwide[2]. Previously classified as an autism spectrum disorder, Rett syndrome became its own diagnosis in the May 2013 edition of the DSM-5.
Comparison of iPSC-derived RTT neurons with those derived from neurotypical subjects revealed numerous structural and functional differences, including a reduction in synapses, spine density, and altered signaling. These traits were noted in developing neurons, which mirror a developmental window before disease onset in RTT individuals that have been previously unstudied. These findings suggest the potential for earlier interventions, including drug screening, diagnosis, and personalized treatment. Since publication, this research has informed models of additional diseases and may contribute significantly to future drug discovery and studies of human development like cited by Drs. Xu and Zhong in their 2013 paper on the success of using stem cell models for drug discovery[3].
Established in 1972, the NIGMS Human Genetic Cell Repository at Coriell houses some of the most widely used (or verbiage that indicates how scientifically impactful they are) cell lines worldwide, encompassing a range of disease states, chromosomal abnormalities, and diverse human populations. Coriell also hosts five additional NIH-funded biobanks, distributes thousands of samples annually, and provides research and biobanking services to scientists internationally.
Further information about the biobank collections is available at coriell.org/1/Browse/Biobanks.
[1] Marchetto MC, Carromeu C, Acab A, Yu D, Yeo GW, Mu Y, Chen G, Gage FH, Muotri AR. A model for neural development and treatment of Rett syndrome using human induced pluripotent stem cells. Cell. 2010 Nov 12;143(4):527-39. doi: 10.1016/j.cell.2010.10.016. PMID: 21074045; PMCID: PMC3003590.
[2] https://www.autismempowerment.org/understanding-autism/signs-symptoms/rett-syndrome/
[3] Xu XH, Zhong Z. Disease modeling and drug screening for neurological diseases using human induced pluripotent stem cells. Acta Pharmacol Sin. 2013 Jun;34(6):755-64. doi: 10.1038/aps.2013.63. Epub 2013 May 20. PMID: 23685955; PMCID: PMC3674515.
