NINDS Application Abstract Pluripotent stem cells were originally isolated from embryos but their utility as tools for research and therapeutic development was severely restricted due to ethical considerations as well as the inability to derive stem cells from subjects with known disorders. Human induced pluripotent stem cells (hiPSC) generated from adult somatic cells were first described in 2007. Since then, hiPSCs have been established from subjects with specific disorders (many with known genotypes) and then differentiated to relevant cell types such as neurons for central nervous system disorders. Using these hiPSC we can create ?disease models in a dish? that can model cell development and disease progression and be used for drug screening and for toxicology testing. However, human genetic diversity has hampered the usefulness of individual hiPSC for disease modeling. Controls often consist of age and sex-matched non-affected family members or other subjects. The CRISPR (clustered regularly-interspaced short palindromic repeats)/Cas system can now generate isogenic hiPSC that will serve as better controls and help eliminate effects that are due to genetic background, thus providing a better understanding of mechanisms of human disease and development. The NINDS Human Cell and Data Repository (NHCDR) was established to collect, derive and distribute human cells such as skin fibroblasts and blood cells and convert these to iPSCs for research on neurodegenerative diseases such as Parkinson?s disease, Alzheimer?s disease, Huntington?s disease, amyotrophic lateral sclerosis, Dystonia and Frontotemporal Degeneration. Since 1998, RUCDR Infinite Biologics (RUCDR) has provided the NIH, private foundations and the global scientific community with the highest quality biomaterials, technical consultation, and logistical support for human genetics research. In 2011, RUCDR began providing its stem cell services to the NIH, including source cell and iPSC banking; iPSC generation; iPSC gene editing; and source cell and iPSC distribution. In 2015, RUCDR successfully competed for the NHCDR and in the past 5 years the catalog has grown to contain 268 FCL lines from 256 subjects and 259 iPSC lines from 132 subjects, including the addition of 7 isogenic pairs of iPSC. During this time RUCDR shipped 458 orders for 1538 cell lines to investigators around the world. The continuing mission of the NHCDR is to work with NINDS investigators and staff on all aspects of study management to collect, process and distribute the highest quality cell lines from human subjects. This effort includes the culturing of fibroblasts from skin biopsies, the isolation of lymphocytes from blood, and the derivation of iPSC lines from both cell types. RUCDR will continue to provide a comprehensive range of quality testing of iPSCs to ensure they conform to the highest standards. If requested, we will also provide additional services to the global community, including the generation of neural stem cells (NSCs) and different types of neurons. RUCDR will continue to exhibit scientific flexibility to grow and adapt to leading best practices in the stem cell field.
iPSC are increasingly utilized in disease modeling, drug discovery, toxicological testing, and clinical applications and the need for high quality, well characterized biomaterials is clear and pressing. The NHCDR and RUCDR will continue to serve the global scientific community by providing source cells, iPSC and isogenic iPSC pairs from subjects with neurological disorders such as Parkinson?s disease, Alzheimer?s disease, Huntington?s disease, amyotrophic lateral sclerosis, Dystonia and Frontotemporal Degeneration.
| Sakurai, Kunie; Kurtz, Andreas; Stacey, Glyn et al. (2016) First Proposal of Minimum Information About a Cellular Assay for Regenerative Medicine. Stem Cells Transl Med 5:1345-1361 |
