Optimizing chimerism level through bone marrow transplantation and irradiation to induce long-term tolerance to composite tissue allotransplantation

Jeng Yee Lin, Feng Chou Tsai, Christopher Glenn Wallace, Wei Chao Huang, Fu Chan Wei, Shuen Kuei Liao

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

Background: Mixed chimerism with long-term composite tissue allotransplant (CTA) acceptance can be achieved through allogeneic bone marrow transplantation (BMT). The present study investigated the optimal chimerism level by giving different irradiation dosages to recipients to induce tolerance to CTA. Methods: Chimera were prepared using Brown-Norway and Lewis rats with strong major histocompatibility complex incompatibility. The Lewis rats received 5 mg antilymphocyte globulin (day -1 and 10) and 16 mg/kg cyclosporine (day 0-10) and were separated into groups 1, 2, 3, 4, and 5 according to the day -1 irradiation dosage: 0, 200, 400, 600, and 950 cGy, respectively. The Lewis rats were then reconstituted with 100 × 106 T-cell-depleted Brown-Norway bone marrow cells (day 0) and received vascularized Brown-Norway-CTA on day 28. Chimerism was assessed monthly by flow cytometry starting on day 28 after BMT. Graft-versus-host disease (GVHD) was assessed clinically and histologically. Results: Chimerism, 4 weeks after BMT, averaged 0.2%, 9.2%, 30.7%, 58%, and 99.3% in groups 1 to 5, respectively. GVHD occurred as follows: groups 1 and 2, none; group 3, 1 case of GVHD; group 4, 7 cases of GVHD (of which 3 died); and group 5, 10 cases of GVHD (of which 6 died). The percentage of long-term CTA acceptance was 0%, 0%, 90%, 70%, and 40% in groups 1 to 5, respectively. The percentage of regulatory T cells was significantly lower in high-chimerism (≥20%, n = 15) than in low-chimerism (

Original languageEnglish
Pages (from-to)487-493
Number of pages7
JournalJournal of Surgical Research
Volume178
Issue number1
DOIs
Publication statusPublished - Nov 2012

Fingerprint

Vascularized Composite Allotransplantation
Chimerism
Bone Marrow Transplantation
Graft vs Host Disease
Norway
Antilymphocyte Serum
Homologous Transplantation
Regulatory T-Lymphocytes
Major Histocompatibility Complex
Bone Marrow Cells
Cyclosporine
Flow Cytometry
T-Lymphocytes

Keywords

  • Bone marrow transplantation
  • Composite tissue allotransplant
  • Graft-versus-host disease
  • T-cell depletion

ASJC Scopus subject areas

  • Surgery

Cite this

Optimizing chimerism level through bone marrow transplantation and irradiation to induce long-term tolerance to composite tissue allotransplantation. / Lin, Jeng Yee; Tsai, Feng Chou; Wallace, Christopher Glenn; Huang, Wei Chao; Wei, Fu Chan; Liao, Shuen Kuei.

In: Journal of Surgical Research, Vol. 178, No. 1, 11.2012, p. 487-493.

Research output: Contribution to journalArticle

Lin, Jeng Yee ; Tsai, Feng Chou ; Wallace, Christopher Glenn ; Huang, Wei Chao ; Wei, Fu Chan ; Liao, Shuen Kuei. / Optimizing chimerism level through bone marrow transplantation and irradiation to induce long-term tolerance to composite tissue allotransplantation. In: Journal of Surgical Research. 2012 ; Vol. 178, No. 1. pp. 487-493.
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AU - Lin, Jeng Yee

AU - Tsai, Feng Chou

AU - Wallace, Christopher Glenn

AU - Huang, Wei Chao

AU - Wei, Fu Chan

AU - Liao, Shuen Kuei

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N2 - Background: Mixed chimerism with long-term composite tissue allotransplant (CTA) acceptance can be achieved through allogeneic bone marrow transplantation (BMT). The present study investigated the optimal chimerism level by giving different irradiation dosages to recipients to induce tolerance to CTA. Methods: Chimera were prepared using Brown-Norway and Lewis rats with strong major histocompatibility complex incompatibility. The Lewis rats received 5 mg antilymphocyte globulin (day -1 and 10) and 16 mg/kg cyclosporine (day 0-10) and were separated into groups 1, 2, 3, 4, and 5 according to the day -1 irradiation dosage: 0, 200, 400, 600, and 950 cGy, respectively. The Lewis rats were then reconstituted with 100 × 106 T-cell-depleted Brown-Norway bone marrow cells (day 0) and received vascularized Brown-Norway-CTA on day 28. Chimerism was assessed monthly by flow cytometry starting on day 28 after BMT. Graft-versus-host disease (GVHD) was assessed clinically and histologically. Results: Chimerism, 4 weeks after BMT, averaged 0.2%, 9.2%, 30.7%, 58%, and 99.3% in groups 1 to 5, respectively. GVHD occurred as follows: groups 1 and 2, none; group 3, 1 case of GVHD; group 4, 7 cases of GVHD (of which 3 died); and group 5, 10 cases of GVHD (of which 6 died). The percentage of long-term CTA acceptance was 0%, 0%, 90%, 70%, and 40% in groups 1 to 5, respectively. The percentage of regulatory T cells was significantly lower in high-chimerism (≥20%, n = 15) than in low-chimerism (

AB - Background: Mixed chimerism with long-term composite tissue allotransplant (CTA) acceptance can be achieved through allogeneic bone marrow transplantation (BMT). The present study investigated the optimal chimerism level by giving different irradiation dosages to recipients to induce tolerance to CTA. Methods: Chimera were prepared using Brown-Norway and Lewis rats with strong major histocompatibility complex incompatibility. The Lewis rats received 5 mg antilymphocyte globulin (day -1 and 10) and 16 mg/kg cyclosporine (day 0-10) and were separated into groups 1, 2, 3, 4, and 5 according to the day -1 irradiation dosage: 0, 200, 400, 600, and 950 cGy, respectively. The Lewis rats were then reconstituted with 100 × 106 T-cell-depleted Brown-Norway bone marrow cells (day 0) and received vascularized Brown-Norway-CTA on day 28. Chimerism was assessed monthly by flow cytometry starting on day 28 after BMT. Graft-versus-host disease (GVHD) was assessed clinically and histologically. Results: Chimerism, 4 weeks after BMT, averaged 0.2%, 9.2%, 30.7%, 58%, and 99.3% in groups 1 to 5, respectively. GVHD occurred as follows: groups 1 and 2, none; group 3, 1 case of GVHD; group 4, 7 cases of GVHD (of which 3 died); and group 5, 10 cases of GVHD (of which 6 died). The percentage of long-term CTA acceptance was 0%, 0%, 90%, 70%, and 40% in groups 1 to 5, respectively. The percentage of regulatory T cells was significantly lower in high-chimerism (≥20%, n = 15) than in low-chimerism (

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KW - T-cell depletion

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