Mesenchymal stem cells facilitate mixed hematopoietic chimerism induction and prevent onset of diabetes in nonobese diabetic mice

Sadaki Asari, Shin Itakura, Jeffrey Rawson, Taihei Ito, Ivan Todorov, Indu Nair, Jonathan Shintaku, Chih Pin Liu, Fouad Kandeel, Yoko S. Mullen

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

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 × 10 BMCs and 5 × 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.

Original languageEnglish
Pages (from-to)846-854
Number of pages9
JournalPancreas
Volume40
Issue number6
DOIs
Publication statusPublished - 01-08-2011

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Inbred NOD Mouse
Chimerism
Mesenchymal Stromal Cells
Bone Marrow Cells
Graft vs Host Disease
Whole-Body Irradiation
Intraperitoneal Injections
Autoimmunity
Inbred C57BL Mouse
Blood Glucose
Anti-Idiotypic Antibodies
Phenotype
Incidence
Therapeutics

All Science Journal Classification (ASJC) codes

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism
  • Hepatology
  • Endocrinology

Cite this

Asari, Sadaki ; Itakura, Shin ; Rawson, Jeffrey ; Ito, Taihei ; Todorov, Ivan ; Nair, Indu ; Shintaku, Jonathan ; Liu, Chih Pin ; Kandeel, Fouad ; Mullen, Yoko S. / Mesenchymal stem cells facilitate mixed hematopoietic chimerism induction and prevent onset of diabetes in nonobese diabetic mice. In: Pancreas. 2011 ; Vol. 40, No. 6. pp. 846-854.
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abstract = "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 × 10 BMCs and 5 × 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.",
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Asari, S, Itakura, S, Rawson, J, Ito, T, Todorov, I, Nair, I, Shintaku, J, Liu, CP, Kandeel, F & Mullen, YS 2011, 'Mesenchymal stem cells facilitate mixed hematopoietic chimerism induction and prevent onset of diabetes in nonobese diabetic mice', Pancreas, vol. 40, no. 6, pp. 846-854. https://doi.org/10.1097/MPA.0b013e318215cdce

Mesenchymal stem cells facilitate mixed hematopoietic chimerism induction and prevent onset of diabetes in nonobese diabetic mice. / Asari, Sadaki; Itakura, Shin; Rawson, Jeffrey; Ito, Taihei; Todorov, Ivan; Nair, Indu; Shintaku, Jonathan; Liu, Chih Pin; Kandeel, Fouad; Mullen, Yoko S.

In: Pancreas, Vol. 40, No. 6, 01.08.2011, p. 846-854.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Mesenchymal stem cells facilitate mixed hematopoietic chimerism induction and prevent onset of diabetes in nonobese diabetic mice

AU - Asari, Sadaki

AU - Itakura, Shin

AU - Rawson, Jeffrey

AU - Ito, Taihei

AU - Todorov, Ivan

AU - Nair, Indu

AU - Shintaku, Jonathan

AU - Liu, Chih Pin

AU - Kandeel, Fouad

AU - Mullen, Yoko S.

PY - 2011/8/1

Y1 - 2011/8/1

N2 - 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 × 10 BMCs and 5 × 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.

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 × 10 BMCs and 5 × 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.

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