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

研究成果: Article査読

7 被引用数 (Scopus)

抄録

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.

本文言語English
ページ(範囲)846-854
ページ数9
ジャーナルPancreas
40
6
DOI
出版ステータスPublished - 08-2011
外部発表はい

All Science Journal Classification (ASJC) codes

  • 内科学
  • 内分泌学、糖尿病および代謝内科学
  • 肝臓学
  • 内分泌学

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