Mesenchymal stem cells facilitate the induction of mixed hematopoietic chimerism and islet allograft tolerance without GVHD in the rat

S. Itakura, S. Asari, J. Rawson, Taihei Ito, I. Todorov, C. P. Liu, N. Sasaki, F. Kandeel, Y. Mullen

Research output: Contribution to journalArticle

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Abstract

Induction of hematopoietic chimerism and subsequent donor-specific immune tolerance via bone marrow transplantation is an ideal approach for islet transplantation to treat type-1 diabetes. We examined the potential of mesenchymal stem cells (MSCs) in the induction of chimerism and islet allograft tolerance without the incidence of graft-versus-host disease (GVHD). Streptozotocin-diabetic rats received a conditioning regimen consisting of antilymphocyte serum and 5 Gy total body irradiation, followed by an intraportal co-infusion of allogeneic MSCs, bone marrow cells (BMCs) and islets. Although all the recipients rejected the islets initially, half of them developed stable mixed chimerism and donor-specific immune tolerance, shown by the engraftment of donor skin and second-set islet transplants and acute rejection of a third-party skin. The engraftment of the primary islet allografts with stable chimerism was achieved by the addition of a 2-week peritransplant administration of 15-deoxyspergualin (DSG). Without MSCs, none of the recipients treated with DSG developed chimerism or reversal of diabetes. GVHD was not observed in any of the recipients infused with MSCs (0/15), whereas it occurred in 4/11 recipients without MSCs. These results indicate a potential use of MSCs for induction of hematopoietic chimerism and subsequent immune tolerance in clinical islet transplantation.

Original languageEnglish
Pages (from-to)336-346
Number of pages11
JournalAmerican Journal of Transplantation
Volume7
Issue number2
DOIs
Publication statusPublished - 01-02-2007

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Transplantation Tolerance
Chimerism
Graft vs Host Disease
Mesenchymal Stromal Cells
Immune Tolerance
Islets of Langerhans Transplantation
Skin
Antilymphocyte Serum
Whole-Body Irradiation
Graft Rejection
Streptozocin
Bone Marrow Transplantation
Type 1 Diabetes Mellitus
Bone Marrow Cells
Allografts
Incidence

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Transplantation
  • Pharmacology (medical)

Cite this

Itakura, S. ; Asari, S. ; Rawson, J. ; Ito, Taihei ; Todorov, I. ; Liu, C. P. ; Sasaki, N. ; Kandeel, F. ; Mullen, Y. / Mesenchymal stem cells facilitate the induction of mixed hematopoietic chimerism and islet allograft tolerance without GVHD in the rat. In: American Journal of Transplantation. 2007 ; Vol. 7, No. 2. pp. 336-346.
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Mesenchymal stem cells facilitate the induction of mixed hematopoietic chimerism and islet allograft tolerance without GVHD in the rat. / Itakura, S.; Asari, S.; Rawson, J.; Ito, Taihei; Todorov, I.; Liu, C. P.; Sasaki, N.; Kandeel, F.; Mullen, Y.

In: American Journal of Transplantation, Vol. 7, No. 2, 01.02.2007, p. 336-346.

Research output: Contribution to journalArticle

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