The NINDS Human Cell and Data Repository (U24 renewal)

Rutgers, The State Univ Of N.J., New Brunswick NJ

Investigators

Linked publications & trials

Abstract

NINDS Application Abstract Human induced pluripotent stem cells (hiPSC) derived through epigenetic reprogramming of adult somatic cells were first described in 2007. Since then, hiPSCs have been established from subjects with specific disorders (many with known genotypes) and subsequently differentiated into somatic cell types such as neurons for research into central nervous system disorders. Using these hiPSC we can create “disease models in a dish” to study disease etiology and progression and for toxicology and drug screening. However, human genomic diversity (i.e., variability in genetic background) limits the utility of individual hiPSC for disease modeling in populations. Controls have often consisted of age and sex-matched non-affected family members or other subjects with the same disorder. However, the CRISPR (clustered regularly-interspaced short palindromic repeats) /Cas gene editing system can now generate isogenic hiPSC that will serve as more precise controls to eliminate effects due to genetic background, thus providing a better understanding of disease etiology and development. The NINDS Human Cell and Data Repository (NHCDR) was established to collect, derive and distribute human somatic cells such as skin fibroblasts and blood cells and reprogram 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 Dementia. In 2015, RUCDR Infinite Biologics® (as part of Rutgers University) successfully competed for the NHCDR award, which was competitively renewed in 2019. In 2020, RUCDR became Infinity-Biologix® (IBX), a privately held company (including the Rutgers University Foundation) with significant new resources, added personnel, new equipment and a larger purpose- designed facility, thereby expanding capabilities to include novel cutting-edge technologies and commercial partnerships. IBX received a grant subaward from Rutgers University to conduct all laboratory, storage and distribution operations of the NHCDR. The rebranding of IBX to SAMPLED in 2021 signified a continuation and broadening of its mission to integrate comprehensive biobanking with state-of-the-art analytical, cellular, and sample management services. Since the award renewal in 2019, we have added 28 fibroblast lines from 14 subjects, 214 iPSC lines from 164 subjects and now have 39 genetically modified cells lines from 18 subjects. Since the initiation of the original award in 2015, we have distributed 5573 cell lines through 1426 orders, an average rate of 800 cell lines per year through nearly 200 orders. The continuing mission of the NHCDR is a collaboration with NINDS investigators and program scientific staff on individual study management, which includes collection, processing and distribution of the highest quality cell lines. This effort includes the culturing of fibroblasts from skin biopsies, the isolation of mononuclear cells from blood, and the derivation of iPSC lines from both. SAMPLED and Rutgers will continue to provide a comprehensive range of iPSC quality testing to ensure conformation to the highest standards. If requested, we can provide additional services to the global scientific and commercial community, including the generation of neural stem cells (NSCs) and different types of neurons and organoids. Our efforts will ensure the scientific flexibility and growth of the NHCDR through continuous adaptation to scientific discoveries and evolving best practices in the stem cell field.