PMID- 21562444 OWN - NLM STAT- MEDLINE DCOM- 20111129 LR - 20211020 IS - 1536-4828 (Electronic) IS - 0885-3177 (Print) IS - 0885-3177 (Linking) VI - 40 IP - 6 DP - 2011 Aug TI - Mesenchymal stem cells facilitate mixed hematopoietic chimerism induction and prevent onset of diabetes in nonobese diabetic mice. PG - 846-54 LID - 10.1097/MPA.0b013e318215cdce [doi] AB - OBJECTIVES: Allogeneic mesenchymal stem cells (MSCs) and bone marrow cells (BMCs) were cotransplanted in nonobese diabetic mice after none myeloablative preconditioning and the development of chimerism, insulitis, diabetes, and graft-versus-host disease (GVHD) were monitored. METHODS: Eight-week-old female nonobese diabetic mice were injected intravenously with 2 x 10 BMCs and 5 x 10 MSCs from C57BL/6 mice after treatment with 2 intraperitoneal injections of anti-CD3 antibody (days -7 and -4) and 3-Gy total body irradiation (day -1). Thereafter, blood glucose and chimerism were monitored on peripheral blood samples. RESULTS: Stable mixed chimerism (3->90% of donor phenotype) was induced in 63.2% of BMCs-MSCs recipients (n = 19) and 45.0% of BMCs-alone recipients (n = 20, P = 0.256). Insulitis was prevented, and euglycemia persisted for more than 18 weeks in 89.5% of BMCs-MSCs recipients including those with less than 3% chimerism and 55% of BM-alone recipients (P < 0.05). In controls, 9.1% of mice receiving preconditioning treatment alone (n = 11) and 16.7% of preconditioned mice receiving only MSCs (n = 12) were nondiabetic. Graft-versus-host disease was not detected in all mice. CONCLUSIONS: Coinjection of MSCs and BMCs increased the success rate in inducing chimerism and preventing insulitis and overt diabetes with no incidence of GVHD. Results also indicated that even microchimerism with less than 3% donor cells is sufficient for blocking autoimmunity. FAU - Asari, Sadaki AU - Asari S AD - Southern California Islet Cell Resources Center, Department of Diabetes, Endocrinology and Metabolism, Beckman Research Institute of City of Hope, Duarte, CA, USA. FAU - Itakura, Shin AU - Itakura S FAU - Rawson, Jeffrey AU - Rawson J FAU - Ito, Taihei AU - Ito T FAU - Todorov, Ivan AU - Todorov I FAU - Nair, Indu AU - Nair I FAU - Shintaku, Jonathan AU - Shintaku J FAU - Liu, Chih-Pin AU - Liu CP FAU - Kandeel, Fouad AU - Kandeel F FAU - Mullen, Yoko S AU - Mullen YS LA - eng GR - U42 RR016607/RR/NCRR NIH HHS/United States GR - U42 RR016607-08/RR/NCRR NIH HHS/United States GR - U42RR16607/RR/NCRR NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PL - United States TA - Pancreas JT - Pancreas JID - 8608542 SB - IM MH - Animals MH - Bone Marrow Transplantation/immunology MH - Diabetes Mellitus, Type 1/*prevention & control MH - Female MH - Graft vs Host Disease/prevention & control MH - Immune Tolerance MH - Islets of Langerhans/cytology/immunology MH - *Mesenchymal Stem Cell Transplantation MH - Mice MH - Mice, Inbred BALB C MH - Mice, Inbred C57BL MH - Mice, Inbred CBA MH - Mice, Inbred NOD MH - *Transplantation Chimera/immunology MH - Transplantation Conditioning MH - Transplantation, Homologous PMC - PMC3138826 MID - NIHMS282173 EDAT- 2011/05/13 06:00 MHDA- 2011/12/13 00:00 PMCR- 2012/08/01 CRDT- 2011/05/13 06:00 PHST- 2011/05/13 06:00 [entrez] PHST- 2011/05/13 06:00 [pubmed] PHST- 2011/12/13 00:00 [medline] PHST- 2012/08/01 00:00 [pmc-release] AID - 10.1097/MPA.0b013e318215cdce [doi] PST - ppublish SO - Pancreas. 2011 Aug;40(6):846-54. doi: 10.1097/MPA.0b013e318215cdce.