Proceedings: Human Leukocyte Antigen Haplo-Homozygous Induced Pluripotent Stem Cell Haplobank Modeled After the California Population: Evaluating Matching in a Multiethnic and Admixed Population

SUMMARY The development of a California-based induced pluripotent stem cell (iPSC) bank based on human leukocyteantigen(HLA)haplotypematchingrepresentsasignificantchallengeandavaluableopportunityfortheadvancementofregenerativemedicine.However,previouslypublishedmodelsofiPSC bankshaveneitheraddressedtheadmixednatureofpopulationslikethatofCalifornianorevaluated thebenefittothepopulationasawhole.WedevelopedanewmodelforevaluatinganiPSChaplobank basedondemographicandimmunogeneticcharacteristicsreflectingCalifornia.Themodelevaluates haplolines or celllines from donors homozygous for a singleHLA-A,HLA-B,HLA-DRB1haplotype. We generatedestimatesofthepercentageofthepopulationmatchedundervariouscombinationsofhaplolines derived from six ancestries (black/African American, American Indian, Asian/Pacific Islander, Hispanic, and white/not Hispanic) and data available from the U.S. Census Bureau, the CaliforniaInstituteforRegenerativeMedicine,andtheNationalMarrowDonorProgram.Themodelincludedboth cis(haplotype-level)andtrans(genotype-level)matchingbetweenamodelediPSChaplobankandthe recipientpopulationfollowing resamplingsimulations.Weshowed thatserving amajority (>50%) of a simulated California population through cis matching would require the creation, redundant storage, and maintenanceofalmost207differenthaplolinesrepresentingthetop 60mostfrequenthaplotypes from each ancestry group. Allowances for trans matching reduced the haplobank to fewer than 141 haplolines found among the top 40 most frequent haplotypes. Finally, we showed that a model optimized, custom haplobank was able to serve a majority of the Californiapopulation with fewer than 80 haplolines. STEM CELLS TRANSLATIONAL MEDICINE 2015;4:413–418