HLA-Based Banking of Human Induced Pluripotent Stem Cells in Saudi Arabia
KAUST DepartmentComputer, Electrical and Mathematical Sciences and Engineering Division, King Abdullah University of Science and Technology (KAUST), Thuwal, Saudi Arabia
Biological and Environmental Science and Engineering (BESE) Division
Computer, Electrical and Mathematical Science and Engineering (CEMSE) Division
Permanent link to this recordhttp://hdl.handle.net/10754/694569
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AbstractHuman iPSCs' derivation and use in clinical studies are transforming medicine. Yet, there is a high cost and long waiting time for autologous iPS-based cellular therapy, and the genetic engineering of hypo-immunogenic iPS cell lines is hampered with numerous hurdles. Therefore, it is increasingly interesting to create cell stocks based on HLA haplotype distribution in a given population. In this study, we assessed the potential of HLA-based iPS banking for the Saudi population. First, we analyzed the HLA database of the Saudi Stem Cell Donor Registry (SSCDR), which contains high-resolution HLA genotype data of 64,315 registered Saudi donors at the time of analysis. We found that only 13 iPS lines would be required to cover 30% of the Saudi population, 39 iPS lines would offer 50% coverage and 596 for more than 90% coverage. Next, As a proof-of-concept, we launched the first HLA-based banking of iPSCs in Saudi Arabia. Using clinically relevant methods, we generated the first iPSC line from a homozygous donor for the most common HLA haplotype in Saudi. The two generated clones expressed pluripotency markers, could be differentiated into all three germ layers, beating cardiomyocytes and neuronal progenitors. To ensure that our reprogramming method generates genetically stable iPSCs, we assessed the mutational burden in the generated clones and the original blood sample from which the iPSCs were derived using whole-genome sequencing. All detected variants were found in the original donor sample and were classified as benign according to current guidelines of the American College of Medical Genetics and Genomics (ACMG). This study sets a road map for introducing iPS-based cell therapy in the Kingdom of Saudi Arabia.
CitationAlowaysi, M., Lehmann, R., Al-Shehri, M., Baadheim, M., Alzahrani, H., Aboalola, D., Zia, A., Malibari, D., Daghestani, M., Alghamdi, K., Haneef, A., Jawdat, D., Hakami, F., Cabrero, D. G., Tegner, J., & Alsayegh, K. (2023). HLA-Based Banking of Human Induced Pluripotent Stem Cells in Saudi Arabia. https://doi.org/10.1101/2023.09.16.557826
SponsorsThis work is funded by KAIMRC grant RJ20/134/J. Additional funding was provided through KAUST’s Smart Health Initiative. We thank King Abdullah International Medical Research Center (KAIMRC) and the Saudi Stem Cell Donor Registry (SSCDR) for facilitating the initiation of HLA-based iPS banking. We thank current, and future donors for their valuable donations.
PublisherCold Spring Harbor Laboratory
Except where otherwise noted, this item's license is described as This is a preprint version of a paper and has not been peer reviewed. Archived with thanks to Cold Spring Harbor Laboratory. The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license. http://creativecommons.org/licenses/by-nc-nd/4.0/