Umbilical Cord Blood Units Cryopreserved in the Public Cord Blood Bank: A Breakthrough in iPSC Haplobanking?

Abstract

The use of induced pluripotent stem cells (iPSCs) is an emerging therapeutic option for precision medicine. Cord blood (CB) cells with lower immunogenicity, fewer genomic changes, and persistent epigenetic memory might be ideal candidates for iPSC production. Based on the human leukocyte antigen (HLA) distribution of cord blood units (CBUs) in the public CB bank, we estimated the coverage of the Korean population with HLA-homozygous iPSCs to repurpose cryopreserved CBUs. We analyzed a total of 27,904 Korean CBUs donated to the public CB bank. Low-to-intermediate resolution typing was performed for HLA-A, -B, and -DRB1 alleles, and individuals possessing homozygous HLA haplotypes were identified by direct counting. Moreover, the matching probabilities for zero-mismatch transplantation were calculated for 27,904 CBUs and 50,000,000 potential Korean patients. Among the preserved CBUs, 15 HLA-A, 40 HLA-B, and 13 HLA-DRB1 alleles as well as 48 homozygous HLA-A-B-DRB1 haplotypes were identified at serological equivalents (2 digits). The 48 identified homozygous haplotypes cumulatively matched 78.18% of the 27,904 Korean CB donors as zero HLA-mismatch iPSC sources. Among the combinations of 1,699 haplotypes with frequencies greater than 0.001%, assuming a population of 50 million, those 48 haplotypes can provide a match for 78.37% of potential Korean recipients. A practicable number of HLA-A, -B, and -DRB1 homozygous iPSC lines derived from CBUs may be an efficient option in allogeneic iPSC therapy because this type of haplobanking may provide cell lines with optimal HLA matching for up to three-quarters of the Korean population.