HLA-based banking of induced pluripotent stem cells in Saudi Arabia

• Published in: Stem cell research & therapy 2023-12, Vol.14 (1), p.374-374, Article 374
• Main Authors: Alowaysi, Maryam, Lehmann, Robert, Al-Shehri, Mohammad, Baadhaim, Moayad, Alzahrani, Hajar, Aboalola, Doaa, Zia, Asima, Malibari, Dalal, Daghestani, Mustafa, Alghamdi, Khaled, Haneef, Ali, Jawdat, Dunia, Hakami, Fahad, Gomez-Cabrero, David, Tegner, Jesper, Alsayegh, Khaled
• Format: Article
• Language: English
• Subjects: Algorithms; Antibodies; Banks (Finance); Biobanking; Cardiomyocytes; Cell differentiation; Cell lines; Cell therapy; Cell- and Tissue-Based Therapy; Datasets; Diagnostic reagents industry; Ethylenediaminetetraacetic acid; Genetic analysis; Genetic engineering; Genetically modified organisms; Genomes; Genomics; Genotypes; Haplotypes; Histocompatibility antigen HLA; HLA-based banking; Homozygote; Humans; Immune response; Immunogenicity; Induced pluripotent stem cells; Induced Pluripotent Stem Cells - metabolism; Inhibitory postsynaptic potentials; IPS-based therapies; Manufacturers; Medical genetics; Medical research; Medicine, Experimental; Military reserves; Neural stem cells; Plasmids; Pluripotency; Population studies; Regenerative Medicine; Saudi Arabia; Stem cell transplantation; Stem cells; Transplantation; Whole genome sequencing
• ISSN: 1757-6512; 1757-6512
• DOI: 10.1186/s13287-023-03612-0

Human iPSCs' derivation and use in clinical studies are transforming medicine. Yet, there is a high cost and long waiting time associated with 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. This study aimed to assess the potential of HLA-based iPS banking for the Saudi population. In this study, we interrogated the HLA database of the Saudi Stem Cell Donor Registry (SSCDR), containing high-resolution HLA genotype data from 64,315 registered Saudi donors at the time of analysis. This database was considered to be a representative sample of the Saudi population. The most frequent HLA haplotypes in the Saudi population were determined, and an in-house developed iterative algorithm was used to identify their HLA matching percentages in the SSCDR database and cumulative coverage. Subsequently, to develop a clinically relevant protocol for iPSCs generation, and to illustrate the applicability of the concept of HLA-based banking for cell therapy purposes, the first HLA-based iPS cell line in Saudi Arabia was generated. Clinically relevant methods were employed to generate the two iPS clones from a homozygous donor for the most prevalent HLA haplotype in the Saudi population. The generated lines were then assessed for pluripotency markers, and their ability to differentiate into all three germ layers, beating cardiomyocytes, and neural progenitors was examined. Additionally, the genetic stability of the HLA-iPS cell lines was verified by comparing the mutational burden in the clones and the original blood sample, using whole-genome sequencing. The standards set by the American College of Medical Genetics and Genomics (ACMG) were used to determine the clinical significance of identified variants. The analysis revealed that the establishment of only 13 iPSC lines would match 30% of the Saudi population, 39 lines would attain 50% coverage, and 596 lines would be necessary for over 90% coverage. The proof-of-concept HLA-iPSCs, which cover 6.1% of the Saudi population, successfully demonstrated pluripotency and the ability to differentiate into various cell types including beating cardiomyocytes and neuronal progenitors. The comprehensive genetic analysis corroborated that all identified variants in the derived iPSCs were inherently present in the original don