Donor and recipient pretransplant conditioning with nonlethal radiation and antilymphocyte serum improves the graft survival in a rat small bowel transplant model

Alexandre Bakonyi, Mariana Berho, Phillip Ruiz, Evangelos P. Misiakos, Manuel Carreno, Werviston De Faria, Antonio Sommariva, Luca A Inverardi, Joshua Miller, Camillo Ricordi, Andreas G. Tzakis

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Background. Lymphoid tissue within the intestinal graft require immunomodulatory strategies to prevent graft versus host disease (GVHD) after transplant. Herein, we evaluate the potential advantage of donor-specific bone marrow infusions in donor and or recipient preconditioned with total body irradiation and or antilymphocyte serum (ALS) on the incidence of GVHD and rejection after small bowel transplantation. Methods. Heterotopic SBTx was performed from DA to Lewis rats and distributed in nine groups: control group GO (n=4) and G1 (n=6) without irradiation; recipients in G2 (n=4) were given 400 rd although in groups 3 (n=5), G4 (n=6), G6 (n=5), G7 (n=5), and G8 (n=6) with 250 rd. Donors in G5 (n=4) and G6 were given 250 rd of total body irradiation 2 hours before intestinal retrieval. Donors and recipients in G7 and donors in G8 additionally received ALS (day -5). G1, 2, 3, 5, 6, 7, and 8 were infused with UDBM and G4 with the same amount of TCDBM. Animals received tacrolimus for 15 days and accessed for rejection, GVHD and for chimerism analysis. Results. High mortality due to GVHD was observed in G2, 3, and 4, and correlated with high levels of donor T cells in recipients blood. G0 and G1 showed early acute rejection with progression toward chronic rejection, in contrast to the preconditioned groups. High and low doses of total body irradiation resulted in allogeneic and in a mixed chimerism, respectively. Decrease in donor chimeric cells after 11 weeks in preconditioned groups was correlated with severe allograft rejection. Conclusion. Donor preconditioning with 250 rd and or ALS combined with recipient preconditioning and donor-specific bone marrow infusions prevented GVHD and resulted in a transient mixed chimerism with inhibition of allograft rejection after small bowel transplantation.

Original languageEnglish
Pages (from-to)983-988
Number of pages6
JournalTransplantation
Volume72
Issue number6
StatePublished - Sep 27 2001

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Antilymphocyte Serum
Graft vs Host Disease
Graft Survival
Chimerism
Radiation
Whole-Body Irradiation
Transplants
Allografts
Transplantation
Bone Marrow
Tacrolimus
Lymphoid Tissue
T-Lymphocytes
Control Groups
Mortality
Incidence

ASJC Scopus subject areas

  • Transplantation
  • Immunology

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Donor and recipient pretransplant conditioning with nonlethal radiation and antilymphocyte serum improves the graft survival in a rat small bowel transplant model. / Bakonyi, Alexandre; Berho, Mariana; Ruiz, Phillip; Misiakos, Evangelos P.; Carreno, Manuel; De Faria, Werviston; Sommariva, Antonio; Inverardi, Luca A; Miller, Joshua; Ricordi, Camillo; Tzakis, Andreas G.

In: Transplantation, Vol. 72, No. 6, 27.09.2001, p. 983-988.

Research output: Contribution to journalArticle

Bakonyi, A, Berho, M, Ruiz, P, Misiakos, EP, Carreno, M, De Faria, W, Sommariva, A, Inverardi, LA, Miller, J, Ricordi, C & Tzakis, AG 2001, 'Donor and recipient pretransplant conditioning with nonlethal radiation and antilymphocyte serum improves the graft survival in a rat small bowel transplant model', Transplantation, vol. 72, no. 6, pp. 983-988.
Bakonyi, Alexandre ; Berho, Mariana ; Ruiz, Phillip ; Misiakos, Evangelos P. ; Carreno, Manuel ; De Faria, Werviston ; Sommariva, Antonio ; Inverardi, Luca A ; Miller, Joshua ; Ricordi, Camillo ; Tzakis, Andreas G. / Donor and recipient pretransplant conditioning with nonlethal radiation and antilymphocyte serum improves the graft survival in a rat small bowel transplant model. In: Transplantation. 2001 ; Vol. 72, No. 6. pp. 983-988.
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abstract = "Background. Lymphoid tissue within the intestinal graft require immunomodulatory strategies to prevent graft versus host disease (GVHD) after transplant. Herein, we evaluate the potential advantage of donor-specific bone marrow infusions in donor and or recipient preconditioned with total body irradiation and or antilymphocyte serum (ALS) on the incidence of GVHD and rejection after small bowel transplantation. Methods. Heterotopic SBTx was performed from DA to Lewis rats and distributed in nine groups: control group GO (n=4) and G1 (n=6) without irradiation; recipients in G2 (n=4) were given 400 rd although in groups 3 (n=5), G4 (n=6), G6 (n=5), G7 (n=5), and G8 (n=6) with 250 rd. Donors in G5 (n=4) and G6 were given 250 rd of total body irradiation 2 hours before intestinal retrieval. Donors and recipients in G7 and donors in G8 additionally received ALS (day -5). G1, 2, 3, 5, 6, 7, and 8 were infused with UDBM and G4 with the same amount of TCDBM. Animals received tacrolimus for 15 days and accessed for rejection, GVHD and for chimerism analysis. Results. High mortality due to GVHD was observed in G2, 3, and 4, and correlated with high levels of donor T cells in recipients blood. G0 and G1 showed early acute rejection with progression toward chronic rejection, in contrast to the preconditioned groups. High and low doses of total body irradiation resulted in allogeneic and in a mixed chimerism, respectively. Decrease in donor chimeric cells after 11 weeks in preconditioned groups was correlated with severe allograft rejection. Conclusion. Donor preconditioning with 250 rd and or ALS combined with recipient preconditioning and donor-specific bone marrow infusions prevented GVHD and resulted in a transient mixed chimerism with inhibition of allograft rejection after small bowel transplantation.",
author = "Alexandre Bakonyi and Mariana Berho and Phillip Ruiz and Misiakos, {Evangelos P.} and Manuel Carreno and {De Faria}, Werviston and Antonio Sommariva and Inverardi, {Luca A} and Joshua Miller and Camillo Ricordi and Tzakis, {Andreas G.}",
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T1 - Donor and recipient pretransplant conditioning with nonlethal radiation and antilymphocyte serum improves the graft survival in a rat small bowel transplant model

AU - Bakonyi, Alexandre

AU - Berho, Mariana

AU - Ruiz, Phillip

AU - Misiakos, Evangelos P.

AU - Carreno, Manuel

AU - De Faria, Werviston

AU - Sommariva, Antonio

AU - Inverardi, Luca A

AU - Miller, Joshua

AU - Ricordi, Camillo

AU - Tzakis, Andreas G.

PY - 2001/9/27

Y1 - 2001/9/27

N2 - Background. Lymphoid tissue within the intestinal graft require immunomodulatory strategies to prevent graft versus host disease (GVHD) after transplant. Herein, we evaluate the potential advantage of donor-specific bone marrow infusions in donor and or recipient preconditioned with total body irradiation and or antilymphocyte serum (ALS) on the incidence of GVHD and rejection after small bowel transplantation. Methods. Heterotopic SBTx was performed from DA to Lewis rats and distributed in nine groups: control group GO (n=4) and G1 (n=6) without irradiation; recipients in G2 (n=4) were given 400 rd although in groups 3 (n=5), G4 (n=6), G6 (n=5), G7 (n=5), and G8 (n=6) with 250 rd. Donors in G5 (n=4) and G6 were given 250 rd of total body irradiation 2 hours before intestinal retrieval. Donors and recipients in G7 and donors in G8 additionally received ALS (day -5). G1, 2, 3, 5, 6, 7, and 8 were infused with UDBM and G4 with the same amount of TCDBM. Animals received tacrolimus for 15 days and accessed for rejection, GVHD and for chimerism analysis. Results. High mortality due to GVHD was observed in G2, 3, and 4, and correlated with high levels of donor T cells in recipients blood. G0 and G1 showed early acute rejection with progression toward chronic rejection, in contrast to the preconditioned groups. High and low doses of total body irradiation resulted in allogeneic and in a mixed chimerism, respectively. Decrease in donor chimeric cells after 11 weeks in preconditioned groups was correlated with severe allograft rejection. Conclusion. Donor preconditioning with 250 rd and or ALS combined with recipient preconditioning and donor-specific bone marrow infusions prevented GVHD and resulted in a transient mixed chimerism with inhibition of allograft rejection after small bowel transplantation.

AB - Background. Lymphoid tissue within the intestinal graft require immunomodulatory strategies to prevent graft versus host disease (GVHD) after transplant. Herein, we evaluate the potential advantage of donor-specific bone marrow infusions in donor and or recipient preconditioned with total body irradiation and or antilymphocyte serum (ALS) on the incidence of GVHD and rejection after small bowel transplantation. Methods. Heterotopic SBTx was performed from DA to Lewis rats and distributed in nine groups: control group GO (n=4) and G1 (n=6) without irradiation; recipients in G2 (n=4) were given 400 rd although in groups 3 (n=5), G4 (n=6), G6 (n=5), G7 (n=5), and G8 (n=6) with 250 rd. Donors in G5 (n=4) and G6 were given 250 rd of total body irradiation 2 hours before intestinal retrieval. Donors and recipients in G7 and donors in G8 additionally received ALS (day -5). G1, 2, 3, 5, 6, 7, and 8 were infused with UDBM and G4 with the same amount of TCDBM. Animals received tacrolimus for 15 days and accessed for rejection, GVHD and for chimerism analysis. Results. High mortality due to GVHD was observed in G2, 3, and 4, and correlated with high levels of donor T cells in recipients blood. G0 and G1 showed early acute rejection with progression toward chronic rejection, in contrast to the preconditioned groups. High and low doses of total body irradiation resulted in allogeneic and in a mixed chimerism, respectively. Decrease in donor chimeric cells after 11 weeks in preconditioned groups was correlated with severe allograft rejection. Conclusion. Donor preconditioning with 250 rd and or ALS combined with recipient preconditioning and donor-specific bone marrow infusions prevented GVHD and resulted in a transient mixed chimerism with inhibition of allograft rejection after small bowel transplantation.

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