Impact of Homozygous Conserved Extended HLA Haplotype on Single Cord Blood Transplantation: Lessons for Induced Pluripotent Stem Cell Banking and Transplantation in Allogeneic Settings

Yasuo Morishima, Satoko Morishima, Makoto Murata, Nobuyoshi Arima, Naoyuki Uchida, Yasuhiro Sugio, Satoshi Takahashi, Yoshiko Matsuhashi, Makoto Onizuka, Tetsuya Eto, Koji Nagafuji, Yasushi Onishi, Masami Inoue, Yoshiko Atsuta, Takahiro Fukuda, Tatsuo Ichinohe, Shunichi Kato, Junya Kanda

Research output: Contribution to journalArticlepeer-review

4 Citations (Scopus)

Abstract

Induced pluripotent stem cells (iPSCs) have been applied to clinical regenerative cell therapy. Recently, an iPSC banking system to collect HLA haplotype (HP) homozygous (homo) cells for iPSC transplantation in allogeneic settings was proposed, and tissue transplantation generated from iPSC through banking has just began. We analyzed 5017 single cord blood transplantation (CBT) pairs with HLA-A, -B, -C, -DRB1 allele typing data and found 39 donor HLA homo donor to patient HLA heterozygous (hetero) pairs. Of note, all 39 HLA homo to hetero pairs engrafted neutrophils, except 1 early death pair, and all 30 assessable pairs engrafted platelets. Acute graft-versus-host disease (GVHD) grades II to IV and grades III to IV occurred in 17 and 3 of 38 assessable pairs, respectively. Competing risk regression analysis revealed a favorable risk of neutrophil engraftment and higher risk of acute GVHD compared with HLA-matched CBTs. Thirty-seven of 39 homo to hetero pairs had conserved extended HLA HPs (HP-1, n = 18; HP-2, n = 8; HP-3, n = 7; HP-4, n = 4; HP-5, n = 1) that were ethnicity-specific, and at least 1 of 2 patient HLA-A, -B, -C, and -DRB1 alleles in each locus were invariably shared with the same donor HP in 35 pairs. These findings confirmed our preliminary results with 6 HLA homo CBTs, and a trend of high incidence of acute GVHD was newly observed. Importantly, they imply the possibility that HLA-homo iPSC transplantation provides favorable engraftment and accordingly imply the merit of banking iPSC with homozygous major conserved extended HLA HPs.

Original languageEnglish
Pages (from-to)132-138
Number of pages7
JournalBiology of Blood and Marrow Transplantation
Volume26
Issue number1
DOIs
Publication statusPublished - 2020 Jan

Keywords

  • Cord blood transplantation
  • HLA haplotype
  • Induced pluripotent stem cell

ASJC Scopus subject areas

  • Hematology
  • Transplantation

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