Constructing a potential HLA haplo-homozygous induced pluripotent stem cell haplobank using data from an umbilical...

Induced pluripotent stem cells (iPSCs) can differentiate into any type of cell and have potential uses in regenerative medicine for the treatment of many diseases. However, reducing immune rejection is a key problem in the application of iPSCs that can be solved by the development of haplobanks containing specially selected iPSC lines.

To study the feasibility of constructing an HLA (human leukocyte antigen)-matched induced pluripotent stem cell haplobank in China, 5421 umbilical cord blood samples were randomly collected from the Umbilical Cord Blood Bank of Zhejiang Province, China. The HLA-A, HLA-B, HLA-C, HLA-DRB1, and HLA-DQB1 loci were genotyped using next-generation sequencing. Using HLA genotype data at the high-resolution level, the number of HLA homozygous donors needed to cover a certain percentage of the Chinese population and the feasibility of constructing a high-matching iPSC haplobank were estimated.

Thirteen HLA-A, -B, and -DRB1 and 11 HLA-A, -B, -C, -DRB1, and -DQB1 haplotype homozygotes were observed among the stored umbilical CB units which were as HLA zero-mismatched iPSC donors cumulatively matched 37.01% and 32.99% of 5421 potential patients respectively. The analysis showed that 100 distinct HLA-A, -B, and -DRB1 and HLA-A, -B, -C, -DRB1, and -DQB1 homozygous haplotypes would cover 72.74% and 67.87% of Chinese populations, respectively, and 600 HLA-A, -B, -C, -DRB1, and -DQB1 homozygous haplotypes would cover more than 90% of Chinese populations. PCA (principal component analysis) of published HLA data from different populations revealed that the frequency of these haplotypes in Asian populations is different from those in European populations.

The results suggested that at least some HLA-homozygous iPSC lines developed from Chinese individuals will not only be useful for covering the Chinese population but will also cover other Asian populations. A high-matching iPSC haplobank generated from umbilical CB units may be an economical and effective option in an allogeneic model of iPSC therapy.