Risk of HLA Homozygous Cord Blood Transplantation: Implications for Induced Pluripotent Stem Cell Banking and Transplantation

on behalf of the Japanese Cord Blood Transplantation Histocompatibility Research Group

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Clinical application of induced pluripotent stem cells (iPS) in autologous settings has just begun. To overcome the high time and cost barriers in the individual production of autologous iPS, the use of allogeneic iPS with a homozygous human leukocyte antigen (HLA) haplotype (HLA-homo HP) has been proposed. Cord blood transplantation (CBT) is a suitable model for evaluating the allogeneic immunogenicity of iPS transplantation from HLA-homo donors. We analyzed 1,374 Japanese single cord blood transplant pairs who were retrospectively typed as HLA-A, -B, -C, -DRB1, -DQB1, and -DPB1. Among these, six pairs with donor HLA homo—patient-HLA hetero (homo-hetero) were found, all of which showed favorable neutrophil engraftment. Multivariate analysis revealed a significantly elevated engraftment risk (HR = 1.59) compared with hetero-hetero pairs with HLA 1-2 locus mismatch (789 pts) and comparative risk (HR = 1.23) compared with hetero-hetero pairs with 0 mismatch (104 pts). These results for CBT with HLA-homo HP cord blood carry an important implication, namely the possibility that HLA-homo iPS transplantation results in favorable engraftment. Furthermore, we obtained detailed information on HLA alleles and haplotypes of HLA-homo. All donor HLA-homo HPs had a common specific ethnicity and high conservation of the HLA region, and one of two patient heterogeneous HPs invariably shared the same HP as donor HLA-homo HP, and another non-shared patient HP was mismatched with 1 to 4 HLA alleles of HLA-A, -B, -C, and -DRB1 loci in the GVH direction. These findings indicate that patients possessing a single common HLA haplotype have a higher chance of yielding HLA-homo iPS. Stem Cells Translational Medicine 2018;7:173–179.

Original languageEnglish
Pages (from-to)173-179
Number of pages7
JournalStem Cells Translational Medicine
Volume7
Issue number2
DOIs
Publication statusPublished - Feb 1 2018

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Induced Pluripotent Stem Cells
Stem Cell Transplantation
HLA Antigens
Fetal Blood
Transplantation
Haplotypes
Alleles
Translational Medical Research

All Science Journal Classification (ASJC) codes

  • Developmental Biology
  • Cell Biology

Cite this

Risk of HLA Homozygous Cord Blood Transplantation : Implications for Induced Pluripotent Stem Cell Banking and Transplantation. / on behalf of the Japanese Cord Blood Transplantation Histocompatibility Research Group.

In: Stem Cells Translational Medicine, Vol. 7, No. 2, 01.02.2018, p. 173-179.

Research output: Contribution to journalArticle

on behalf of the Japanese Cord Blood Transplantation Histocompatibility Research Group. / Risk of HLA Homozygous Cord Blood Transplantation : Implications for Induced Pluripotent Stem Cell Banking and Transplantation. In: Stem Cells Translational Medicine. 2018 ; Vol. 7, No. 2. pp. 173-179.
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abstract = "Clinical application of induced pluripotent stem cells (iPS) in autologous settings has just begun. To overcome the high time and cost barriers in the individual production of autologous iPS, the use of allogeneic iPS with a homozygous human leukocyte antigen (HLA) haplotype (HLA-homo HP) has been proposed. Cord blood transplantation (CBT) is a suitable model for evaluating the allogeneic immunogenicity of iPS transplantation from HLA-homo donors. We analyzed 1,374 Japanese single cord blood transplant pairs who were retrospectively typed as HLA-A, -B, -C, -DRB1, -DQB1, and -DPB1. Among these, six pairs with donor HLA homo—patient-HLA hetero (homo-hetero) were found, all of which showed favorable neutrophil engraftment. Multivariate analysis revealed a significantly elevated engraftment risk (HR = 1.59) compared with hetero-hetero pairs with HLA 1-2 locus mismatch (789 pts) and comparative risk (HR = 1.23) compared with hetero-hetero pairs with 0 mismatch (104 pts). These results for CBT with HLA-homo HP cord blood carry an important implication, namely the possibility that HLA-homo iPS transplantation results in favorable engraftment. Furthermore, we obtained detailed information on HLA alleles and haplotypes of HLA-homo. All donor HLA-homo HPs had a common specific ethnicity and high conservation of the HLA region, and one of two patient heterogeneous HPs invariably shared the same HP as donor HLA-homo HP, and another non-shared patient HP was mismatched with 1 to 4 HLA alleles of HLA-A, -B, -C, and -DRB1 loci in the GVH direction. These findings indicate that patients possessing a single common HLA haplotype have a higher chance of yielding HLA-homo iPS. Stem Cells Translational Medicine 2018;7:173–179.",
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AU - on behalf of the Japanese Cord Blood Transplantation Histocompatibility Research Group

AU - Morishima, Yasuo

AU - Azuma, Fumihiro

AU - Kashiwase, Koichi

AU - Matsumoto, Kayoko

AU - Orihara, Takeshi

AU - Yabe, Hiromasa

AU - Kato, Shunichi

AU - Kato, Koji

AU - Kato, Koji

AU - Mori, Tetsuo

AU - Nakajima, Kazunori

AU - Morishima, Satoko

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AU - Takanashi, Minoko

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