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

Abstract Background 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 developmen...

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Main Authors: Ji He, Yanmin He, Qigang Zhan, Zhipan Wu, Qi Sheng, Wei Zhang, Faming Zhu
Format: Article
Language:English
Published: BMC 2025-02-01
Series:Stem Cell Research & Therapy
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Online Access:https://doi.org/10.1186/s13287-025-04159-y
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author Ji He
Yanmin He
Qigang Zhan
Zhipan Wu
Qi Sheng
Wei Zhang
Faming Zhu
author_facet Ji He
Yanmin He
Qigang Zhan
Zhipan Wu
Qi Sheng
Wei Zhang
Faming Zhu
author_sort Ji He
collection DOAJ
description Abstract Background 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. Methods 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. Results 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. Conclusion 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.
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spelling doaj-art-391c76724e8c45ab8b19b56978fd9d6c2025-02-09T12:15:37ZengBMCStem Cell Research & Therapy1757-65122025-02-0116111010.1186/s13287-025-04159-yConstructing a potential HLA haplo-homozygous induced pluripotent stem cell haplobank using data from an umbilical cord blood bankJi He0Yanmin He1Qigang Zhan2Zhipan Wu3Qi Sheng4Wei Zhang5Faming Zhu6Blood Center of Zhejiang ProvinceBlood Center of Zhejiang ProvinceUmbilical Cord Blood Bank of Zhejiang ProvinceBlood Center of Zhejiang ProvinceUmbilical Cord Blood Bank of Zhejiang ProvinceBlood Center of Zhejiang ProvinceBlood Center of Zhejiang ProvinceAbstract Background 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. Methods 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. Results 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. Conclusion 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.https://doi.org/10.1186/s13287-025-04159-yiPSCs induced pluripotent stem cellsHLA homozygoteHaplobankingUmbilical cord blood
spellingShingle Ji He
Yanmin He
Qigang Zhan
Zhipan Wu
Qi Sheng
Wei Zhang
Faming Zhu
Constructing a potential HLA haplo-homozygous induced pluripotent stem cell haplobank using data from an umbilical cord blood bank
Stem Cell Research & Therapy
iPSCs induced pluripotent stem cells
HLA homozygote
Haplobanking
Umbilical cord blood
title Constructing a potential HLA haplo-homozygous induced pluripotent stem cell haplobank using data from an umbilical cord blood bank
title_full Constructing a potential HLA haplo-homozygous induced pluripotent stem cell haplobank using data from an umbilical cord blood bank
title_fullStr Constructing a potential HLA haplo-homozygous induced pluripotent stem cell haplobank using data from an umbilical cord blood bank
title_full_unstemmed Constructing a potential HLA haplo-homozygous induced pluripotent stem cell haplobank using data from an umbilical cord blood bank
title_short Constructing a potential HLA haplo-homozygous induced pluripotent stem cell haplobank using data from an umbilical cord blood bank
title_sort constructing a potential hla haplo homozygous induced pluripotent stem cell haplobank using data from an umbilical cord blood bank
topic iPSCs induced pluripotent stem cells
HLA homozygote
Haplobanking
Umbilical cord blood
url https://doi.org/10.1186/s13287-025-04159-y
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