Induction of tolerance in quadruple chimeric mice

Tian Xue Fan, Hiroko Hisha, Tie Nan Jin, Kikuya Sugiura, Muneo Inaba, Guo Xiang Yang, Qing Li, Xiao Li Wang, Chang Ye Song, Yun Ze Cui, Qiang Li, Yuming Zhang, Xiao Guang Zhang, Hong Xue Fan, Susumu Ikehara

Research output: Contribution to journalArticlepeer-review

1 Scopus citations


Human cord blood (CB) contains hematopoietic stem cells and progenitors. Because the major limitation to a widespread use of CB for transplantation lies in its limited volume, it is necessary to combine the CB from several donors. In this study, we show that lethally irradiated mice can be reconstituted with the injection of a mixture of T cell-depleted bone marrow cells (BMCs; total, 3 × 106) obtained from three fully allogeneic mouse strains in two different mouse combinations. A higher survival rate was obtained in the triple injection group than in mice injected with BMCs (1 × 10 6) obtained from a single mouse strain. In the mixed chimeric mice, three kinds of donor-type and recipient-type cells were detected in all the hematopoietic organs 1 month after bone marrow transplantation (BMT). Mixed-lymphocyte reaction showed that the tolerance to both recipient-type and donor-type major histocompatibility complex determinants was induced in the chimeric mice. In the peripheral blood (PB) of these mice, only one type of cells from the three different donor strains became dominant in most chimeric mice and reached a stable level about 4 months after BMT. Polymerase chain reaction analyses, however, revealed that the skins from all the donors were accepted even when no cells with their phenotypes could be detected in the PB. These results suggest that both hemato-lymphoid reconstitution and stable tolerance to not only the recipient strain but also all the donor strains can be achieved in chimeric mice, indicating the possibility of mixed CB transplantation in humans.

Original languageEnglish
Pages (from-to)683-695
Number of pages13
JournalStem Cells
Issue number5
StatePublished - 2004
Externally publishedYes


  • Bone marrow transplantation
  • Cord blood cells
  • Reconstitution


Dive into the research topics of 'Induction of tolerance in quadruple chimeric mice'. Together they form a unique fingerprint.

Cite this