HLA-Based Banking of Human Induced Pluripotent Stem Cells in Saudi Arabia

Abstract

Human 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.