Correlation between allograft survival and chimeric state after bone marrow infusion in rat small bowel transplantation

Alexandre Bakonyi Neto, Camillo Ricordi, Claudio F. Feo, Alberto Porcu, Evangelos P. Misiakos, Carlos Gandia, Phillip Ruiz, Mariana Bertho, Manuel Carreno, Violet Esquenazi, Joshua Miller, Andreas G. Tzakis

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Methods to enhance natural microchimerism, which occurs after any successful organ transplant, are currently explored using unmodified donor bone marrow both in experimental and in clinical trials. Because of the potential immunomodulatory effects of donor bone marrow cells, we performed this study to evaluate the effect of single and multiple donor-specific bone marrow infusions (DSBMI) on chimerism and small bowel allograft survival in a fully histoincompatible rat model. Forty-five male DA rats and 45 female Lewis rats were used as donors and recipients, respectively, for a heterotopic small bowen transplant. Animals were separated into 10 groups according to the number of bone marrow infusions and immunosuppressive protocol used. Control groups (groups 1 and 2) did not receive any bone marrow infusion, groups 3 and 4 received one infusion at day 0 (150 x 106 cells), groups 5 and 6 received two infusions at days 0 and 4 (75 x 106 cells each), groups 7 and 8 received two infusions at days 4 and 10 (75 x 106 cells each), and groups 9 and 10 received five infusions at days 4, 10, 15, 20 and 25 (30 x 106 cells each). Animals in groups 1, 3, 5, 7 and 9 were immunosuppressed with 0.5 mg/kg FK506 while the remaining groups were immunosuppressed with 1 mg/kg FK506, from day 0 to 4 after transplant. Every 15 days, the chimeric state was determined by flow cytometry in order to detect cells expressing DA rat class I antigen, and small bowel biopsies were obtained from ileostomies. Animals in all groups showed minimal to moderate acute rejection at day 15 after transplant, however, vascular rejection (vasculitis, arteritis) was observed in only bone marrow groups (100% in 0.5 mg/kg and 42.1% in 1 mg/kg FK506 groups). On day 30, 58.3% of bone-marrow- infused animals and 66.6% of controls showed severe acute and early chronic rejection. The chimeric levels varied from 0 to 12% after transplant and were significantly higher in bone-marrow-infused groups compared with controls (p < 0.05). We conclude that modulation of immune response with short-course immunosuppression and a single or multiple DSBMI did not improve allograft or recipient survival. The inability to achieve a stable chimeric state did not allow us to determine the effect of chimerism on graft and recipient survival after small bowel transplantation.

Original languageEnglish
Pages (from-to)67-73
Number of pages7
JournalPediatric Transplantation
Volume3
Issue number1
DOIs
StatePublished - Feb 1 1999

Fingerprint

Allografts
Transplantation
Bone Marrow
Chimerism
Transplants
Tacrolimus
Arteritis
Ileostomy
Histocompatibility Antigens Class I
Graft Survival
Immunosuppressive Agents
Vasculitis
Bone Marrow Cells
Immunosuppression
Blood Vessels
Flow Cytometry
Clinical Trials
Biopsy
Control Groups

Keywords

  • Bone marrow infusion
  • Rejection
  • Small bowel transplantation

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Transplantation

Cite this

Correlation between allograft survival and chimeric state after bone marrow infusion in rat small bowel transplantation. / Bakonyi Neto, Alexandre; Ricordi, Camillo; Feo, Claudio F.; Porcu, Alberto; Misiakos, Evangelos P.; Gandia, Carlos; Ruiz, Phillip; Bertho, Mariana; Carreno, Manuel; Esquenazi, Violet; Miller, Joshua; Tzakis, Andreas G.

In: Pediatric Transplantation, Vol. 3, No. 1, 01.02.1999, p. 67-73.

Research output: Contribution to journalArticle

Bakonyi Neto, A, Ricordi, C, Feo, CF, Porcu, A, Misiakos, EP, Gandia, C, Ruiz, P, Bertho, M, Carreno, M, Esquenazi, V, Miller, J & Tzakis, AG 1999, 'Correlation between allograft survival and chimeric state after bone marrow infusion in rat small bowel transplantation', Pediatric Transplantation, vol. 3, no. 1, pp. 67-73. https://doi.org/10.1034/j.1399-3046.1999.00010.x
Bakonyi Neto, Alexandre ; Ricordi, Camillo ; Feo, Claudio F. ; Porcu, Alberto ; Misiakos, Evangelos P. ; Gandia, Carlos ; Ruiz, Phillip ; Bertho, Mariana ; Carreno, Manuel ; Esquenazi, Violet ; Miller, Joshua ; Tzakis, Andreas G. / Correlation between allograft survival and chimeric state after bone marrow infusion in rat small bowel transplantation. In: Pediatric Transplantation. 1999 ; Vol. 3, No. 1. pp. 67-73.
@article{644ef7cdddd14ebb9b3591d4a9229f5c,
title = "Correlation between allograft survival and chimeric state after bone marrow infusion in rat small bowel transplantation",
abstract = "Methods to enhance natural microchimerism, which occurs after any successful organ transplant, are currently explored using unmodified donor bone marrow both in experimental and in clinical trials. Because of the potential immunomodulatory effects of donor bone marrow cells, we performed this study to evaluate the effect of single and multiple donor-specific bone marrow infusions (DSBMI) on chimerism and small bowel allograft survival in a fully histoincompatible rat model. Forty-five male DA rats and 45 female Lewis rats were used as donors and recipients, respectively, for a heterotopic small bowen transplant. Animals were separated into 10 groups according to the number of bone marrow infusions and immunosuppressive protocol used. Control groups (groups 1 and 2) did not receive any bone marrow infusion, groups 3 and 4 received one infusion at day 0 (150 x 106 cells), groups 5 and 6 received two infusions at days 0 and 4 (75 x 106 cells each), groups 7 and 8 received two infusions at days 4 and 10 (75 x 106 cells each), and groups 9 and 10 received five infusions at days 4, 10, 15, 20 and 25 (30 x 106 cells each). Animals in groups 1, 3, 5, 7 and 9 were immunosuppressed with 0.5 mg/kg FK506 while the remaining groups were immunosuppressed with 1 mg/kg FK506, from day 0 to 4 after transplant. Every 15 days, the chimeric state was determined by flow cytometry in order to detect cells expressing DA rat class I antigen, and small bowel biopsies were obtained from ileostomies. Animals in all groups showed minimal to moderate acute rejection at day 15 after transplant, however, vascular rejection (vasculitis, arteritis) was observed in only bone marrow groups (100{\%} in 0.5 mg/kg and 42.1{\%} in 1 mg/kg FK506 groups). On day 30, 58.3{\%} of bone-marrow- infused animals and 66.6{\%} of controls showed severe acute and early chronic rejection. The chimeric levels varied from 0 to 12{\%} after transplant and were significantly higher in bone-marrow-infused groups compared with controls (p < 0.05). We conclude that modulation of immune response with short-course immunosuppression and a single or multiple DSBMI did not improve allograft or recipient survival. The inability to achieve a stable chimeric state did not allow us to determine the effect of chimerism on graft and recipient survival after small bowel transplantation.",
keywords = "Bone marrow infusion, Rejection, Small bowel transplantation",
author = "{Bakonyi Neto}, Alexandre and Camillo Ricordi and Feo, {Claudio F.} and Alberto Porcu and Misiakos, {Evangelos P.} and Carlos Gandia and Phillip Ruiz and Mariana Bertho and Manuel Carreno and Violet Esquenazi and Joshua Miller and Tzakis, {Andreas G.}",
year = "1999",
month = "2",
day = "1",
doi = "10.1034/j.1399-3046.1999.00010.x",
language = "English",
volume = "3",
pages = "67--73",
journal = "Pediatric Transplantation",
issn = "1397-3142",
publisher = "Wiley-Blackwell",
number = "1",

}

TY - JOUR

T1 - Correlation between allograft survival and chimeric state after bone marrow infusion in rat small bowel transplantation

AU - Bakonyi Neto, Alexandre

AU - Ricordi, Camillo

AU - Feo, Claudio F.

AU - Porcu, Alberto

AU - Misiakos, Evangelos P.

AU - Gandia, Carlos

AU - Ruiz, Phillip

AU - Bertho, Mariana

AU - Carreno, Manuel

AU - Esquenazi, Violet

AU - Miller, Joshua

AU - Tzakis, Andreas G.

PY - 1999/2/1

Y1 - 1999/2/1

N2 - Methods to enhance natural microchimerism, which occurs after any successful organ transplant, are currently explored using unmodified donor bone marrow both in experimental and in clinical trials. Because of the potential immunomodulatory effects of donor bone marrow cells, we performed this study to evaluate the effect of single and multiple donor-specific bone marrow infusions (DSBMI) on chimerism and small bowel allograft survival in a fully histoincompatible rat model. Forty-five male DA rats and 45 female Lewis rats were used as donors and recipients, respectively, for a heterotopic small bowen transplant. Animals were separated into 10 groups according to the number of bone marrow infusions and immunosuppressive protocol used. Control groups (groups 1 and 2) did not receive any bone marrow infusion, groups 3 and 4 received one infusion at day 0 (150 x 106 cells), groups 5 and 6 received two infusions at days 0 and 4 (75 x 106 cells each), groups 7 and 8 received two infusions at days 4 and 10 (75 x 106 cells each), and groups 9 and 10 received five infusions at days 4, 10, 15, 20 and 25 (30 x 106 cells each). Animals in groups 1, 3, 5, 7 and 9 were immunosuppressed with 0.5 mg/kg FK506 while the remaining groups were immunosuppressed with 1 mg/kg FK506, from day 0 to 4 after transplant. Every 15 days, the chimeric state was determined by flow cytometry in order to detect cells expressing DA rat class I antigen, and small bowel biopsies were obtained from ileostomies. Animals in all groups showed minimal to moderate acute rejection at day 15 after transplant, however, vascular rejection (vasculitis, arteritis) was observed in only bone marrow groups (100% in 0.5 mg/kg and 42.1% in 1 mg/kg FK506 groups). On day 30, 58.3% of bone-marrow- infused animals and 66.6% of controls showed severe acute and early chronic rejection. The chimeric levels varied from 0 to 12% after transplant and were significantly higher in bone-marrow-infused groups compared with controls (p < 0.05). We conclude that modulation of immune response with short-course immunosuppression and a single or multiple DSBMI did not improve allograft or recipient survival. The inability to achieve a stable chimeric state did not allow us to determine the effect of chimerism on graft and recipient survival after small bowel transplantation.

AB - Methods to enhance natural microchimerism, which occurs after any successful organ transplant, are currently explored using unmodified donor bone marrow both in experimental and in clinical trials. Because of the potential immunomodulatory effects of donor bone marrow cells, we performed this study to evaluate the effect of single and multiple donor-specific bone marrow infusions (DSBMI) on chimerism and small bowel allograft survival in a fully histoincompatible rat model. Forty-five male DA rats and 45 female Lewis rats were used as donors and recipients, respectively, for a heterotopic small bowen transplant. Animals were separated into 10 groups according to the number of bone marrow infusions and immunosuppressive protocol used. Control groups (groups 1 and 2) did not receive any bone marrow infusion, groups 3 and 4 received one infusion at day 0 (150 x 106 cells), groups 5 and 6 received two infusions at days 0 and 4 (75 x 106 cells each), groups 7 and 8 received two infusions at days 4 and 10 (75 x 106 cells each), and groups 9 and 10 received five infusions at days 4, 10, 15, 20 and 25 (30 x 106 cells each). Animals in groups 1, 3, 5, 7 and 9 were immunosuppressed with 0.5 mg/kg FK506 while the remaining groups were immunosuppressed with 1 mg/kg FK506, from day 0 to 4 after transplant. Every 15 days, the chimeric state was determined by flow cytometry in order to detect cells expressing DA rat class I antigen, and small bowel biopsies were obtained from ileostomies. Animals in all groups showed minimal to moderate acute rejection at day 15 after transplant, however, vascular rejection (vasculitis, arteritis) was observed in only bone marrow groups (100% in 0.5 mg/kg and 42.1% in 1 mg/kg FK506 groups). On day 30, 58.3% of bone-marrow- infused animals and 66.6% of controls showed severe acute and early chronic rejection. The chimeric levels varied from 0 to 12% after transplant and were significantly higher in bone-marrow-infused groups compared with controls (p < 0.05). We conclude that modulation of immune response with short-course immunosuppression and a single or multiple DSBMI did not improve allograft or recipient survival. The inability to achieve a stable chimeric state did not allow us to determine the effect of chimerism on graft and recipient survival after small bowel transplantation.

KW - Bone marrow infusion

KW - Rejection

KW - Small bowel transplantation

UR - http://www.scopus.com/inward/record.url?scp=0343778859&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0343778859&partnerID=8YFLogxK

U2 - 10.1034/j.1399-3046.1999.00010.x

DO - 10.1034/j.1399-3046.1999.00010.x

M3 - Article

VL - 3

SP - 67

EP - 73

JO - Pediatric Transplantation

JF - Pediatric Transplantation

SN - 1397-3142

IS - 1

ER -