PMID- 17283484 OWN - NLM STAT- MEDLINE DCOM- 20070320 LR - 20230124 IS - 1600-6135 (Print) IS - 1600-6135 (Linking) VI - 7 IP - 2 DP - 2007 Feb TI - Mesenchymal stem cells facilitate the induction of mixed hematopoietic chimerism and islet allograft tolerance without GVHD in the rat. PG - 336-46 AB - 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. FAU - Itakura, S AU - Itakura S AD - Southern California Islet Cell Resource Center, Department of Diabetes, Endocrinology and Metabolism, Duarte, CA, USA. sitakura@coh.org FAU - Asari, S AU - Asari S FAU - Rawson, J AU - Rawson J FAU - Ito, T AU - Ito T FAU - Todorov, I AU - Todorov I FAU - Liu, C-P AU - Liu CP FAU - Sasaki, N AU - Sasaki N FAU - Kandeel, F AU - Kandeel F FAU - Mullen, Y AU - Mullen Y LA - eng PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't PL - United States TA - Am J Transplant JT - American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons JID - 100968638 SB - IM MH - Animals MH - Bone Marrow Transplantation/*methods MH - Cells, Cultured MH - *Chimera MH - Diabetes Mellitus, Experimental/surgery MH - Diabetes Mellitus, Type 1/therapy MH - Graft Rejection/immunology/pathology MH - Graft vs Host Disease/immunology/*prevention & control MH - *Hematopoietic Stem Cell Transplantation MH - Immune Tolerance/*immunology MH - Immunosuppression Therapy MH - Islets of Langerhans Transplantation/*immunology/pathology MH - Killer Cells, Natural/immunology/pathology MH - Male MH - *Mesenchymal Stem Cell Transplantation MH - Rats MH - Rats, Inbred BN MH - Rats, Inbred Lew MH - Transplantation Tolerance/immunology MH - Transplantation, Homologous/immunology EDAT- 2007/02/07 09:00 MHDA- 2007/03/21 09:00 CRDT- 2007/02/07 09:00 PHST- 2007/02/07 09:00 [pubmed] PHST- 2007/03/21 09:00 [medline] PHST- 2007/02/07 09:00 [entrez] AID - S1600-6135(22)14579-X [pii] AID - 10.1111/j.1600-6143.2006.01643.x [doi] PST - ppublish SO - Am J Transplant. 2007 Feb;7(2):336-46. doi: 10.1111/j.1600-6143.2006.01643.x.