Donor-derived bone marrow transfusion produces mixed chimerism and promotes a Th2 shift in Th1/Th2 balance in rat heterotopic small bowel transplantation

Dig Liver Dis. 2012 Dec;44(12):988-94. doi: 10.1016/j.dld.2012.08.002. Epub 2012 Sep 4.

Abstract

Background and aim: In this study, we investigated immunomodulatory effects of donor-derived bone marrow transfusion in rat heterotopic small bowel transplantation.

Methods: Rat heterotopic segmental small bowel transplantation models (male Brown Norway to female Lewis) were established. The recipients were randomly divided into control group (pute small bowel transplantation), tacrolimus group (small bowel transplantation plus oral tacrolimus) and small bowel transplantation plus oral tacrolimus and intraportal infusion of donor-derived bone marrow cells group. We investigated the survival time, graft pathologic injuries and rejection grade by haematoxylin-eosin staining, serum IL-2 and IL-10 detection by enzyme labelled immunosorbent assay after small bowel transplantation. The recipients mixed chimerism were observed by detecting sex-determining region of Y chromosome gene in blood, liver, spleen and intestine by using real-time polymerase chain reaction and fluorescence in situ hybridization.

Results: Bone marrow cells group showed a superior survival than the other groups, accompanied by milder pathologic injuries and lower rejection grade, decreasing serum IL-2 and increasing serum IL-10. The recipient chimerism rate in blood, liver, spleen and intestine in bone marrow cells group was significantly higher than the other groups.

Conclusion: Transfusion of donor-derived bone marrow cells via portal vein induces mixed chimerism in rats after small bowel transplantation, which may promote a Th2 shift in Th1/Th2 balance and facilitate the induction of immune tolerance.

Publication types

  • Evaluation Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biomarkers / blood
  • Bone Marrow Transplantation / immunology*
  • Chimerism*
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Graft Rejection / genetics
  • Graft Rejection / immunology
  • Graft Rejection / prevention & control*
  • Graft Survival / genetics
  • Graft Survival / immunology
  • Immunosuppressive Agents / therapeutic use
  • In Situ Hybridization, Fluorescence
  • Interleukin-10 / blood
  • Interleukin-2 / blood
  • Intestine, Small / immunology
  • Intestine, Small / transplantation*
  • Kaplan-Meier Estimate
  • Male
  • Random Allocation
  • Rats
  • Real-Time Polymerase Chain Reaction
  • Tacrolimus / therapeutic use
  • Th1-Th2 Balance*
  • Transplantation Tolerance / genetics*
  • Transplantation Tolerance / immunology
  • Transplantation, Heterotopic

Substances

  • Biomarkers
  • Immunosuppressive Agents
  • Interleukin-2
  • Interleukin-10
  • Tacrolimus