Usefulness of the Hematopoietic Stem Cell Donor Pool as a Source of HLA-Homozygous Induced Pluripotent Stem Cells for Haplobanking: Combined Analysis of the Cord Blood Inventory and Bone Marrow Donor Registry.

Abstract

Induced pluripotent stem cells (iPSCs) have opened up unprecedented opportunities for novel therapeutic options for precision medicine. Hematopoietic stem cell (HSC) donor pools with previously determined HLA types may be ideal sources for iPSC production. Based on the HLA distribution of cryopreserved cord blood units (CBUs) and registered bone marrow (BM) donors, we estimated how much of the Korean population could be covered by HLA-homozygous iPSCs. We analyzed a total of 143,866 Korean HSC donors (27,904 CBUs and 115,962 BM donors). Each donor sample was typed for the HLA-A, -B, and -DRB1 alleles at low to intermediate resolution by DNA-based molecular techniques: PCR sequence-specific oligonucleotide (PCR-SSOP), PCR with sequence-specific primers (PCR-SSP) and PCR with sequence-based typing (PCR-SBT). We also identified individuals possessing homozygous HLA haplotypes by direct counting. The matching probabilities for zero-mismatch transplantation were calculated for 143,866 Koreans and 50 million potential Korean patients. Among the HSC donor pool, 17 HLA-A alleles, 41 HLA-B alleles, and 13 HLA-DRB1 alleles, as well as 128 homozygous HLA-A-B-DRB1 haplotypes, were identified at serologic equivalents, and those haplotypes cumulatively matched 93.20% of the 143,866 Korean donors as zero HLA-mismatch iPSC sources. Among the combinations of 2,056 haplotypes with frequencies ≥ 0.001% in a population of 50 million, those 128 homozygous haplotypes can provide 93.65% coverage for potential Korean recipients. Haplobanking of a reasonable number of HLA-A, -B, and -DRB1 homozygous iPSC lines derived from CBUs and cells of registered BM donors may be an efficient option for allogenic iPSC therapy.