Tissue Banking and Management
There is growing interest in generating HLA homozygous Induced Pluripotent Stem Cell (iPSC) lines from HLA haplotype homozygous donors. In allotransplantation, reducing immune rejection is a key problem can be solved by the development of haplobank containing specially selected iPSC lines to provide HLA matching products to large portions of the population. Here, to study the feasibility of constructing highly matched induced pluripotent stem cell haplobank, we estimated the number of HLA homozygous donors needed to cover a certain percentage of the Chinese population using 5421 cord blood (CB) HLA -A, -B, -C, -DRB1, -DQB1 high-resolution HLA typing data.
Study
Design/Methods:
5421 specimens from the Zhejiang Cord Blood Bank were genotyped for HLA -A, -B, -C, -DRB1 and-DQB1 loci using next generation sequencing method（This study was approved by the Ethical Review Committee of Zhejiang Blood Center, China.). The frequency of alleles, haplotype estimation and linkage disequilibrium analysis were performed with the Arlequin software 3.5.2.2. The matching probability was calculated with homozygous donors as assumed iPS donors and 5421 random donors as assumed patients. If the assumed patients’ phenotype contained all the alleles present in the iPS cell’s phenotype, this was considered a match. From the top 10 haplotypes, the population coverage was estimated using the criteria of zero mismatches in HLA -A, -B, -C, -DRB1, -DQB1 and relatedness of the Chinese HLA homozygous iPSC lines to other populations was analyzed.
Results/Findings:
A total of 3326 distinct HLA -A, -B, -C, -DRB1, -DQB1 haplotypes with frequency over 0.1% were estimated. 11 HLA -A, -B, -C, -DRB1, -DQB1 haplotypes homozygotes would cumulatively match 32.99% of 5421 potential patients as HLA zero-mismatch iPSC donors. The analysis showed that 100 distinct HLA -A, -B, -C, -DRB1, -DQB1 homozygous haplotypes would cover 67.87% of Chinese populations and 600 homozygous haplotypes would cover above 90% of Chinese populations. Among the top 10 haplotypes in Chinese, there were two haplotypes are also present both in Korean and Japanese populations, three were only present in Korean, the same haplotypes was not seen in Spanish population. These results suggest that at least some of the HLA-homozygous iPSC lines from Chinese will not only be useful to cover the Chinese population but also will cover other Asian populations.
Conclusions:
High-matching iPSC haplobank generated from CBUs may be an economical and effective option in the allogeneic model of iPSC therapy. Using banked cord blood units to create an iPSC haplobank that will cover a significant percentage of the Chinese population for future advanced therapy replacement strategies.