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Induction of Tolerance in Quadruple Chimeric Mice

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 reconstit... Full description

Journal Title: STEM CELLS September 2004, Vol.22(5), pp.683-695
Main Author: Fan, Tian‐Xue
Other Authors: Hisha, Hiroko , Jin, Tie‐Nan , Sugiura, Kikuya , Inaba, Muneo , Yang, Guo‐Xiang , Li, Qing , Wang, Xiao‐Li , Song, Chang‐Ye , Cui, Yun‐Ze , Li, Qiang , Zhang, Yuming , Zhang, Xiao‐Guang , Fan, Hong‐Xue , Ikehara, Susumu
Format: Electronic Article Electronic Article
Language: English
Subjects:
ID: ISSN: 1066-5099 ; E-ISSN: 1549-4918 ; DOI: 10.1634/stemcells.22-5-683
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recordid: wj10.1634/stemcells.22-5-683
title: Induction of Tolerance in Quadruple Chimeric Mice
format: Article
creator:
  • Fan, Tian‐Xue
  • Hisha, Hiroko
  • Jin, Tie‐Nan
  • Sugiura, Kikuya
  • Inaba, Muneo
  • Yang, Guo‐Xiang
  • Li, Qing
  • Wang, Xiao‐Li
  • Song, Chang‐Ye
  • Cui, Yun‐Ze
  • Li, Qiang
  • Zhang, Yuming
  • Zhang, Xiao‐Guang
  • Fan, Hong‐Xue
  • Ikehara, Susumu
subjects:
  • Cord Blood Cells
  • Bone Marrow Transplantation
  • Reconstitution
ispartof: STEM CELLS, September 2004, Vol.22(5), pp.683-695
description: 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 × 10) 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) 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.
language: eng
source:
identifier: ISSN: 1066-5099 ; E-ISSN: 1549-4918 ; DOI: 10.1634/stemcells.22-5-683
fulltext: fulltext
issn:
  • 1066-5099
  • 10665099
  • 1549-4918
  • 15494918
url: Link


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titleInduction of Tolerance in Quadruple Chimeric Mice
creatorFan, Tian‐Xue ; Hisha, Hiroko ; Jin, Tie‐Nan ; Sugiura, Kikuya ; Inaba, Muneo ; Yang, Guo‐Xiang ; Li, Qing ; Wang, Xiao‐Li ; Song, Chang‐Ye ; Cui, Yun‐Ze ; Li, Qiang ; Zhang, Yuming ; Zhang, Xiao‐Guang ; Fan, Hong‐Xue ; Ikehara, Susumu
ispartofSTEM CELLS, September 2004, Vol.22(5), pp.683-695
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subjectCord Blood Cells ; Bone Marrow Transplantation ; Reconstitution
descriptionHuman 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 × 10) 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) 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.
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titleInduction of Tolerance in Quadruple Chimeric Mice
descriptionHuman 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 × 10) 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) 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.
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abstractHuman 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 × 10) 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) 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.
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pubJohn Wiley & Sons, Ltd.
doi10.1634/stemcells.22-5-683
pages683-695
date2004-09