Proceedings: Human Leukocyte Antigen Haplo-Homozygous Induced Pluripotent Stem Cell Haplobank Modeled After the California Population: Evaluating Matching in a Multiethnic and Admixed Population
Authors: Pappas Derek James , Gourraud Pierre-Antoine , Le Gall Caroline , Laurent Julie , Trounson Alan , DeWitt Natalie , Talib Sohel 
Published: April 2015

Summary

The development of a California-based induced pluripotent stem cell (iPSC) bank based on human leukocyte antigen (HLA) haplotype matching represents a significant challenge and a valuable opportunity for the advancement of regenerative medicine. However, previously published models of iPSC banks have neither addressed the admixed nature of populations like that of California nor evaluated the benefit to the population as a whole. We developed a new model for evaluating an iPSC haplobank based on demographic and immunogenetic characteristics reflecting California. The model evaluates haplolines or cell lines from donors homozygous for a single HLA-A, HLA-B, HLA-DRB1 haplotype. We generated estimates of the percentage of the population matched under various combinations of haplolines 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 California Institute for Regenerative Medicine, and the National Marrow Donor Program. The model included both cis (haplotype-level) and trans (genotype-level) matching between a modeled iPSC haplobank and the recipient population following resampling simulations. We showed that serving a majority (&gt;50%) of a simulated California population through cis matching would require the creation, redundant storage, and maintenance of almost 207 different haplolines representing the top 60 most frequent haplotypes 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 California population with fewer than 80 haplolines.

Significance
Induced pluripotent stem cell (iPSC) technology offers the promise of cellular therapies for a wide variety of diseases and injuries. Should these clinical trials be successful, it will be necessary to consider what it would take to deliver these novel treatments to the large numbers of patients who will need them. The use of allogeneic iPSC cell lines for derivation of grafts for transplantation has been considered; however, in order to avoid graft rejection by the allogeneic host, immunological compatibility between graft and host need to be considered. Creation of a haplobank of iPSC lines homozygous for a variety of HLA types, representative of different geographic populations and ethnic groups, could simplify HLA matching and provide matches for reasonable percentages of target populations and extend iPSC-derived therapies beyond the autologous setting. To that end, the rationale for the current study was that the genetic diversity of California's population might be a considerable advantage in establishing a representative “world bank” compared with banking from countries in which populations have more uniform ancestry.